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The History of Cancer: Discovery and Treatment

History of cancer.

  • Modern Advances

Frequently Asked Questions

Cancer may have been “discovered” and written about thousands of years ago. However, the disease itself has actually existed since before the evolution of humans.

It was first documented in Egypt about 5,000 years ago. Since that time, people from cultures all over the world have written about the disease and its potential treatments.

This article will look at what we know about the history of cancer. It will also talk about how our understanding of what causes cancer and how it can be treated has changed over time.

  • 3000 BCE : The world’s earliest known mention of cancer was found in a papyrus document from ancient Egypt. It described tumors found in the breast . The cancer was treated by destroying the tissue with a hot instrument called “the fire drill”—a technique we now call “cauterization.” Some writings have shown that the ancient Egyptians could distinguish between cancerous (malignant) and noncancerous (benign) tumors.
  • 460 BCE : In ancient Greece, Hippocrates thought there were four fluids in the body that influenced health: blood, phlegm , yellow bile , and black bile. He believed that having too much black bile in a part of the body caused cancer. For the next 1,400 years, people believed cancer was caused by too much black bile.
  • 1628 : William Harvey, physician to King James I of England, dissected animals and human cadavers to learn more about how the body worked. When he published a book about the circulatory system, it upended ancient ideas and opened the door for more research on the workings of the human body.
  • 1761 : Giovanni Morgagni of Padua published a book based on hundreds of autopsies he had performed on former patients of his, looking at both their clinical symptoms in life and his postmortem observations of their organs. This laid the groundwork for modern autopsies to determine the cause of someone’s death.
  • 1775: A British surgeon named Percivall Pott discovered that testicular cancer was common in chimney sweeps. This was the first time a cancer was connected to an environmental cause.
  • 17th century : The discovery of the lymphatic system led to new ideas about cancer. The lymphatic system includes the tissues, vessels, and organs that move a substance called lymph around your body. Lymph is an important part of your immune system. When the lymphatic system was discovered, it brought about the possibility that problems in this part of the body could cause cancer. This idea was called the lymph theory. It replaced Hippocrates’ theory about black bile and cancer.
  • 1838 : Johannes Mueller, a German pathologist, showed that cancer is made of cells, not lymph. Mueller’s student, physician Rudolf Virchow, figured out that all our cells—even cancerous ones—come from other cells. However, he thought cancer spread in the body “like a liquid.”
  • 1860 : A German surgeon named Karl Thiersch was the first person to prove that cancer spread through malignant cells.

How Cancer Was Named

Although most people cite Hippocrates as the first person to use the word cancer, he actually used the Greek words karkinos and karkinoma when he wrote about tumors. These words were related to the Greek word for “crab” because Hippocrates thought the insides of the tumors looked like crabs.

The Roman physician Celsus was the first to translate the word into the Latin word “cancer.”

20th Century to Present Day

The 20th century was an exciting time in cancer research. Carcinogens,  chemotherapy , radiation therapy, and better ways to diagnose cancer were all discovered in these years. Some of the most important discoveries of the 20th century include:

  • 1915 : Katsusaburo Yamagiwa and Koichi Ichikawa at Tokyo University applied coal tar to the skin of rabbits, inducing cancer and showing that some substances are carcinogens or cancer-causing.
  • 1962 : James Watson and Frances Crick won a Nobel Prize for discovering the chemical structure of DNA.
  • 1970s : Scientists discover oncogenes and tumor suppressor genes.
  • 1981: Japanese professor Takeshi Hirayama published the first research linking lung cancer to second-hand smoke.  
  • 1982: Baruch S. Blumberg helped develop a vaccine against hepatitis B, a cause of liver cancer.
  • 1989: The first gene therapy cancer treatments began to evolve.
  • 1994: Scientists discovered the BRCA1 gene. This was the first known gene found to predispose a person to developing breast or ovarian cancer.
  • 1999: Jan Walboomers and Michele Manos found evidence implicating human papillomavirus (HPV) to 99.7% percent of cervical cancers.

Today, we are still learning more about cancer. We have found ways to prevent and treat some forms of cancer and even cure others. Clinical trials have allowed scientists to test new ways to find and treat cancer. Some of this century’s notable discoveries so far include:

  • 2006: The first vaccine against the HPV virus was approved in the United States.
  • 2009: Researchers find that immunotherapy improves cure rates for children with neuroblastoma.
  • 2011: Low-dose computed tomography (CT) scans help reduce lung cancer deaths by finding early-stage cancer in high-risk people.
  • 2016: Researchers find evidence that a type of gene therapy called (CAR) T can produce remission in some people with B-cell hematologic cancers.
  • 2021: The OncoKB, a genetic variant database, was recognized by the FDA as a tool for predicting drug responses in people with cancer. This will help oncologists find the best individual treatments for people with specific types of cancer.

Humans have known about cancer for millennia, but our modern understanding of cancer has only developed in the past few centuries. New advancements are being made all the time, and huge leaps have been made in the last few decades alone. This bodes well for the future of cancer treatments and therapies.

A Word From Verywell

How we look at cancer and its treatments has significantly changed in the last few centuries. Even decades ago, we had limited treatment options and less research. Learning about cancer and treatment history can be interesting when seeing how far we’ve come in such a short time. With new research and discoveries occurring all the time, the future of cancer research is an exciting topic.

Cancer has been around since humanity began recording its history and likely existed even before that time. The oldest description of cancer originates from Egypt around 3000 BC in a text called the Edwin Smith Papyrus, which also describes the Egyptian process of tumor removal using a method of cauterization.

Cancer was treated throughout most of the 1800s using surgery to remove cancerous tumors and affected organs. The discovery of X-rays in 1895 by a physicist named Wilhelm Konrad Roentgen helped to diagnose cancer cases and helped pave the way for radiation therapy.

In 1838, a pathologist known as Johannes Müller showed that cancer cells are what make up cancer. Before this, it was believed that cancer was made up of lymph.

It was first treated by surgery, although early physicians realized that cancer often came back after surgery.

The German chemist Paul Ehrlich started working with drugs to treat infectious diseases in the early 1900s. He coined the term “chemotherapy” to describe the use of chemicals to treat disease. He wasn’t very optimistic about medicine to treat cancer, though.

Cancer is more common with age, and more people are living longer, increasing the risk of cancer. A better metric of progress is the cancer death rate, which is decreasing, indicating that we are developing better treatments for cancer.

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By Jaime R. Herndon, MS, MPH Jaime Herndon is a freelance health/medical writer with over a decade of experience writing for the public.

Book cover

Handbook of Oncobiology: From Basic to Clinical Sciences pp 1–29 Cite as

History, Evolution, Milestones in Cancer Research and Treatment

  • Indu Sharma   ORCID: orcid.org/0000-0001-9846-9787 4 ,
  • Anuradha Sharma   ORCID: orcid.org/0000-0001-5975-1456 4 ,
  • Reena Tomer   ORCID: orcid.org/0000-0003-1133-763X 4 ,
  • Neha Negi   ORCID: orcid.org/0000-0002-1902-7081 4 &
  • Ranbir Chander Sobti 5  
  • Living reference work entry
  • First Online: 15 July 2023

43 Accesses

The historical findings of patients with cancer from ancient Egyptian and Greek civilizations support the millennium long medical history of cancer. However, the disease at that time was mostly treated with not so effective radical surgery and cautery, making death the ultimate outcome of cancer patients. Over the centuries, various breakthrough discoveries have not only reformed the cancer detection but also contributed to the development of more effective therapeutic approaches. The most significant of them was the unearthing of cytotoxic antitumor drugs and the inception of chemotherapy. Since then, an exponential progress has been witnessed over the time about new cancer drugs. Another revolution in the field of oncology was targeted therapy with the development of specific drugs for some molecular targets involved in vital neoplastic processes. Collectively, chemotherapy and targeted therapy have definitely enhanced not only the survival rate but also the quality of life of cancer patients. In present times, genetic engineering studies have amplified the further advancements of cancer biology by utilizing monoclonal antibodies and immune checkpoint inhibitors specifically for advanced or metastatic tumors. Hence, cancer research has continuously grown with an intend to develop newer and better therapeutic approaches for cancer. Most recent, artificial intelligence and precision medicine are certainly going to bring a new revolution in the field of medical oncology.

  • Chemotherapy
  • Radiotherapy
  • Targeted Therapy

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Sharma, I., Sharma, A., Tomer, R., Negi, N., Sobti, R.C. (2023). History, Evolution, Milestones in Cancer Research and Treatment. In: Sobti, R.C., Ganguly, N.K., Kumar, R. (eds) Handbook of Oncobiology: From Basic to Clinical Sciences. Springer, Singapore. https://doi.org/10.1007/978-981-99-2196-6_2-1

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  • Published: 05 February 2020

The evolutionary history of 2,658 cancers

  • Moritz Gerstung 1 , 2 , 3   na1 ,
  • Clemency Jolly 4   na1 ,
  • Ignaty Leshchiner 5   na1 ,
  • Stefan C. Dentro 3 , 4 , 6   na1 ,
  • Santiago Gonzalez 1   na1 ,
  • Daniel Rosebrock 5 ,
  • Thomas J. Mitchell 3 , 7 ,
  • Yulia Rubanova 8 , 9 ,
  • Pavana Anur 10 ,
  • Kaixian Yu 11 ,
  • Maxime Tarabichi 3 , 4 ,
  • Amit Deshwar 8 , 9 ,
  • Jeff Wintersinger 8 , 9 ,
  • Kortine Kleinheinz 12 , 13 ,
  • Ignacio Vázquez-García 3 , 7 ,
  • Kerstin Haase 4 ,
  • Lara Jerman 1 , 14 ,
  • Subhajit Sengupta 15 ,
  • Geoff Macintyre 16 ,
  • Salem Malikic 17 , 18 ,
  • Nilgun Donmez 17 , 18 ,
  • Dimitri G. Livitz 5 ,
  • Marek Cmero 19 , 20 ,
  • Jonas Demeulemeester 4 , 21 ,
  • Steven Schumacher 5 ,
  • Yu Fan 11 ,
  • Xiaotong Yao 22 , 23 ,
  • Juhee Lee 24 ,
  • Matthias Schlesner 12 ,
  • Paul C. Boutros 8 , 25 , 26 ,
  • David D. Bowtell 27 ,
  • Hongtu Zhu 11 ,
  • Gad Getz 5 , 28 , 29 , 30 ,
  • Marcin Imielinski 22 , 23 ,
  • Rameen Beroukhim 5 , 31 ,
  • S. Cenk Sahinalp 18 , 32 ,
  • Yuan Ji 15 , 33 ,
  • Martin Peifer 34 ,
  • Florian Markowetz 16 ,
  • Ville Mustonen 35 ,
  • Ke Yuan 16 , 36 ,
  • Wenyi Wang 11 ,
  • Quaid D. Morris 8 , 9 ,
  • PCAWG Evolution & Heterogeneity Working Group ,
  • Paul T. Spellman 10   na2 ,
  • David C. Wedge 6 , 37   na2 ,
  • Peter Van Loo 4 , 21   na2 &

PCAWG Consortium

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  • Cancer genomics
  • Computational biology and bioinformatics
  • Molecular evolution

An Author Correction to this article was published on 25 January 2023

This article has been updated

Cancer develops through a process of somatic evolution 1 , 2 . Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes 3 . Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) 4 , we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

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history of cancer research

Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients

Diletta Fontana, Ilaria Crespiatico, … Daniele Ramazzotti

history of cancer research

Pan-cancer analysis of whole genomes

The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium

history of cancer research

The repertoire of mutational signatures in human cancer

Ludmil B. Alexandrov, Jaegil Kim, … PCAWG Consortium

Similar to the evolution in species, the approximately 10 14 cells in the human body are subject to the forces of mutation and selection 1 . This process of somatic evolution begins in the zygote and only comes to rest at death, as cells are constantly exposed to mutagenic stresses, introducing 1–10 mutations per cell division 2 . These mutagenic forces lead to a gradual accumulation of point mutations throughout life, observed in a range of healthy tissues 5 , 6 , 7 , 8 , 9 , 10 , 11 and cancers 12 . Although these mutations are predominantly selectively neutral passenger mutations, some are proliferatively advantageous driver mutations 13 . The types of mutation in cancer genomes are well studied, but little is known about the times when these lesions arise during somatic evolution and where the boundary between normal evolution and cancer progression should be drawn.

Sequencing of bulk tumour samples enables partial reconstruction of the evolutionary history of individual tumours, based on the catalogue of somatic mutations they have accumulated 3 , 14 , 15 . These inferences include timing of chromosomal gains during early somatic evolution 16 , phylogenetic analysis of late cancer evolution using matched primary and metastatic tumour samples from individual patients 17 , 18 , 19 , 20 , and temporal ordering of driver mutations across many samples 21 , 22 .

The PCAWG Consortium has aggregated whole-genome sequencing data from 2,658 cancers 4 , generated by the ICGC and TCGA, and produced high-accuracy somatic variant calls, driver mutations, and mutational signatures 4 , 23 , 24 (Methods and Supplementary Information ).

Here, we leverage the PCAWG dataset to characterize the evolutionary history of 2,778 cancer samples from 2,658 unique donors across 38 cancer types. We infer timing and patterns of chromosomal evolution and learn typical sequences of mutations across samples of each cancer type. We then define broad periods of tumour evolution and examine how drivers and mutational signatures vary between these epochs. Using clock-like mutational processes, we map mutation timing estimates into approximate real time. Combined, these analyses allow us to sketch out the typical evolutionary trajectories of cancer, and map them in real time relative to the point of diagnosis.

Reconstructing the life history of tumours

The genome of a cancer cell is shaped by the cumulative somatic aberrations that have arisen during its evolutionary past, and part of this history can be reconstructed from whole-genome sequencing data 3 (Fig. 1a ). Initially, each point mutation occurs on a single chromosome in a single cell, which gives rise to a lineage of cells bearing the same mutation. If that chromosomal locus is subsequently duplicated, any point mutation on this allele preceding the gain will subsequently be present on the two resulting allelic copies, unlike mutations succeeding the gain, or mutations on the other allele. As sequencing data enable the measurement of the number of allelic copies, one can define categories of early and late clonal variants, preceding or succeeding copy number gains, as well as unspecified clonal variants, which are common to all cancer cells, but cannot be timed further. Lastly, we identify subclonal mutations, which are present in only a subset of cells and have occurred after the most recent common ancestor (MRCA) of all cancer cells in the tumour sample ( Supplementary Information ).

figure 1

a , Principles of timing mutations and copy number gains based on whole-genome sequencing. The number of sequencing reads reporting point mutations can be used to discriminate variants as early or late clonal (green or purple, respectively) in cases of specific copy number gains, as well as clonal (blue) or subclonal (red) in cases without. b , Annotated point mutations in one sample based on VAF (top), copy number (CN) state and structural variants (middle), and resulting timing estimates (bottom). LOH, loss of heterozygosity. c , Overview of the molecular timing distribution of copy number gains across cancer types. Pie charts depict the distribution of the inferred mutation time for a given copy number gain in a cancer type. Green denotes early clonal gains, with a gradient to purple for late gains. The size of each chart is proportional to the recurrence of this event. Abbreviations for each cancer type are defined in  Supplementary Table 1 . d , Heat maps representing molecular timing estimates of gains on different chromosome arms ( x axis) for individual samples ( y axis) for selected tumour types. e , Temporal patterns of two near-diploid cases illustrating synchronous gains (top) and asynchronous gains (bottom). f , Left, distribution of synchronous and asynchronous gain patterns across samples, split by WGD status. Uninformative samples have too few or too small gains for accurate timing. Right, the enrichment of synchronous gains in near-diploid samples is shown by systematic permutation tests. g , Proportion of copy number segments ( n  = 90,387) with secondary gains. Error bars denote 95% credible intervals. ND, near diploid. h , Distribution of the relative latency of n  = 824 secondary gains with available timing information, scaled to the time after the first gain and aggregated per chromosome.

Source data

The ratio of duplicated to non-duplicated mutations within a gained region can be used to estimate the time point when the gain happened during clonal evolution, referred to here as molecular time, which measures the time of occurrence relative to the total number of (clonal) mutations. For example, there would be few, if any, co-amplified early clonal mutations if the gain had occurred right after fertilization, whereas a gain that happened towards the end of clonal tumour evolution would contain many duplicated mutations 14 (Fig. 1a , Methods).

These analyses are illustrated in Fig. 1b . As expected, the variant allele frequencies (VAFs) of somatic point mutations cluster around the values imposed by the purity of the sample, local copy number configuration and identified subclonal populations. The depicted clear cell renal cell carcinoma has gained chromosome arm 5q at an early molecular time as part of an unbalanced translocation t(3p;5q), which confirms the notion that this lesion often occurs in adolescence in this cancer type 16 . At a later time point, the sample underwent a whole genome duplication (WGD) event, duplicating all alleles, including the derivative chromosome, in a single event, as evidenced by the mutation time estimates of all copy number gains clustering around a single time point, independently of the exact copy number state.

Timing patterns of copy number gains

To systematically examine the mutational timing of chromosomal gains throughout the evolution of tumours in the PCAWG dataset, we applied this analysis to the 2,116 samples with copy number gains suitable for timing ( Supplementary Information ). We find that chromosomal gains occur across a wide range of molecular times (median molecular time 0.60, interquartile range (IQR) 0.10–0.87), with systematic differences between tumour types, whereas within tumour types, different chromosomes typically show similar distributions (Fig. 1c , Extended Data Figs. 1 , 2 , Supplementary Information ). In glioblastoma and medulloblastoma, a substantial fraction of gains occurs early in molecular time. By contrast, in lung cancers, melanomas and papillary kidney cancers, gains arise towards the end of the molecular timescale. Most tumour types, including breast, ovarian and colorectal cancers, show relatively broad periods of chromosomal instability, indicating a very variable timing of gains across samples.

There are, however, certain tumour types with consistently early or late gains of specific chromosomal regions. Most pronounced is glioblastoma, in which 90% of tumours contain single copy gains of chromosome 7, 19 or 20 (Fig. 1c, d ). Notably, these gains are consistently timed within the first 10% of molecular time, which suggests that they arise very early in a patient’s lifetime. In the case of trisomy 7, typically less than 3 out of 600 single nucleotide variants (SNVs) on the whole chromosome precede the gain (Extended Data Fig. 3a, b ). On the basis of a mutation rate of µ  = 4.8 × 10 −10 to 3.0 × 10 −9 SNVs per base pair per division 25 , this indicates that the trisomy occurs within the first 6–39 cell divisions, suggesting a possible early developmental origin, in agreement with somatic mosaicisms observed in the healthy brain 26 . Similarly, the duplications leading to isochromosome 17q in medulloblastoma are timed exceptionally early (Extended Data Fig. 3c, d ).

Notably, we observed that gains in the same tumour often appear to occur at a similar molecular time, pointing towards punctuated bursts of copy number gains involving most gained segments (Fig. 1e ). Although this is expected in tumours with WGD (Fig. 1b ), it may seem surprising to observe synchronous gains in near-diploid tumours, particularly as only 6% of co-amplified chromosomal segments were linked by a direct inter-chromosomal structural variant. Still, synchronous gains are frequent, occurring in 57% (468 out of 815) of informative near-diploid tumours, 61% more frequently than expected by chance ( P  < 0.01, permutation test; Fig. 1f ). Because most arm-level gains increment the allele-specific copy number by 1 (80–90%; Fig. 1g ), it seems that these gains arise through mis-segregation of single copies during anaphase. This notion is further supported by the observation that in about 85% of segments with two gains of the same allele, the second gain appears with noticeable latency after the first (Fig. 1h ). Therefore, the extensive chromosome-scale copy number aberrations observed in many cancer genomes are seemingly caused by a limited number of events—possibly by merotelic attachments of chromosomes to multipolar mitotic spindles 27 , or as a consequence of negative selection of individual aneuploidies 28 —offering an explanation for observations of punctuated evolution in breast and colorectal cancer 29 , 30 .

Timing of point mutations in driver genes

As outlined above, point mutations (SNVs and insertions and deletions (indels)) can be qualitatively assigned to different epochs, allowing the timing of driver mutations. Out of the 47 million point mutations in 2,583 unique samples, 22% were early clonal, 7% late clonal, 53% unspecified clonal and 17% subclonal (Fig. 2a ). Among a panel of 453 cancer driver genes, 5,913 oncogenic point mutations were identified 4 , of which 29% were early clonal, 5% late clonal, 56% unspecified clonal and 8% subclonal. It thus emerges that common drivers are enriched in the early clonal and unspecified clonal categories and depleted in the late clonal and subclonal ones, indicating a preferential early timing (Fig. 2b ). For example, driver mutations in TP53 and KRAS are 12 and 8 times enriched in early clonal stages, respectively. For TP53 , this trend is independent of tumour type (Fig. 2c ). Mutations in PIK3CA are two times more frequently clonal than expected, and non-coding changes near the TERT gene are three times more frequently early clonal.

figure 2

a , Top, distribution of point mutations over different mutation periods in n  = 2,778 samples. Middle, timing distribution of driver mutations in the 50 most recurrent lesions across n  = 2,583 white listed samples from unique donors. Bottom, distribution of driver mutations across cancer types; colour as defined in the inset. b , Relative timing of the 50 most recurrent driver lesions, calculated as the odds ratio of early versus late clonal driver mutations versus background, or clonal versus subclonal. Error bars denote 95% confidence intervals derived from bootstrap resampling. Odds ratios overlapping 1 in less than 5% of bootstrap samples are considered significant (coloured). The underlying number of samples with a given mutation is shown in a . c , Relative timing of TP53 mutations across cancer types, as in b . The number of samples is defined in the x -axis labels. d , Estimated number of unique lesions (genes) contributing 50% of all driver mutations in different timing epochs across n  = 2,583 unique samples, containing n  = 5,756 driver mutations with available timing information. Error bars denote the range between 0 and 1 pseudocounts; bars denote the average of the two values. NA, not applicable; NS, not significant.

Aggregating the clonal status of all driver point mutations over time reveals an increased diversity of driver genes mutated at later stages of tumour development: 50% of all early clonal driver mutations occur in just 9 genes, whereas 50% of late and subclonal mutations occur in approximately 35 different genes each, a nearly fourfold increase (Fig. 2d ). Consistent with previous studies of individual tumour types 31 , 32 , 33 , 34 , these results suggest that, in general, the very early events in cancer evolution occur in a constrained set of common drivers, and a more diverse array of drivers is involved in late tumour development.

Relative timing of somatic driver events

Although timing estimates of individual events reflect evolutionary periods that differ from one sample to another, they define in part the order in which driver mutations and copy number alterations have occurred in each sample (Fig. 3a–d ). As confirmed by simulations, aggregating these orderings across samples defines a probabilistic ranking of lesions (Fig. 3a ), recapitulating whether each mutation occurs preferentially early or late during tumour evolution (Extended Data Figs. 4 , 5 , Supplementary Information ).

figure 3

a , Schematic representation of the ordering process. b – d , Examples of individual patient trajectories (partial ordering relationships), the constituent data for the ordering model process. e – g , Preferential ordering diagrams for colorectal adenocarcinoma (ColoRect–AdenoCA) ( e ), pancreatic neuroendocrine cancer (Panc–Endocrine) ( f ) and glioblastoma (CNS–GBM) ( g ). Probability distributions show the uncertainty of timing for specific events in the cohort. Events with odds above 10 (either earlier or later) are highlighted. The prevalence of the event type in the cohort is displayed as a bar plot on the right.

In colorectal adenocarcinoma, for example, we find APC mutations to have the highest odds of occurring early, followed by KRAS , loss of 17p and TP53 , and SMAD4 (Fig. 3b , e). Whole-genome duplications occur after tumours have accumulated several driver mutations, and many chromosomal gains and losses are typically late. These results are in agreement with the classical APC-KRAS-TP53 progression model of Fearon and Vogelstein 35 , but add considerable detail.

In many cancer types, the sequence of events during cancer progression has not previously been determined in detail. For example, in pancreatic neuroendocrine cancers, we find that many chromosomal losses, including those of chromosomes 2, 6, 11 and 16, are among the earliest events, followed by driver mutations in MEN1 and DAXX (Fig. 3c, f ). WGD events occur later, after many of these tumours have reached a pseudo-haploid state due to widespread chromosomal losses. In glioblastoma, we find that the loss of chromosome 10, and driver mutations in TP53 and EGFR are very early, often preceding early gains of chromosomes 7, 19 and 20 (Fig. 3d, g ). Mutations in the TERT promoter tend to occur at early to intermediate time points, whereas other driver mutations and copy number changes tend to be later events.

Across cancer types, we typically find TP53 mutations among the earliest events, as well as losses of chromosome 17 ( Supplementary Information ). WGD events usually have an intermediate ranking, and most copy number changes occur later. Losses typically precede gains, and consistent with the results above, common drivers typically occur before rare drivers.

Timing of mutational signatures

The cancer genome is shaped by various mutational processes over its lifetime, stemming from exogenous and cell-intrinsic DNA damage, and error-prone DNA replication, leaving behind characteristic mutational spectra, termed mutational signatures 24 , 36 . Stratifying mutations by their clonal allelic status, we find evidence for a changing mutational spectrum between early and late clonal time points in 29% (530 out of 1,852) of informative samples ( P  < 0.05, Bonferroni-adjusted likelihood-ratio test), typically changing the spectrum by 19% (median absolute difference; range 4–66%) (Fig. 4a, b , Extended Data Fig. 6 ). Similarly, 30% of informative samples (729 out of 2,387) displayed changes of their mutation spectrum between the clonal and subclonal state, with median difference of 21% (range 3–72%). Combined, the mutation spectrum changes throughout tumour evolution in 40% of samples (1,069 out of 2,688).

figure 4

a , Example of tumours with substantial changes between mutation spectra of early (left) and late (right) clonal time points. The attribution of mutations to the most characteristic signatures are shown. b , Example of clonal-to-subclonal mutation spectrum change. c , Fold changes between relative proportions of early and late clonal mutations attributed to individual mutational signatures. Points are coloured by tissue type. Data are shown for samples ( n  = 530) with measurable changes in their overall mutation spectra and restricted to signatures active in at least 10 samples. Box plots demarcate the first and third quartiles of the distribution, with the median shown in the centre and whiskers covering data within 1.5× the IQR from the box. d , Fold changes between clonal and subclonal periods in samples ( n  = 729) with measurable changes in their mutation spectra, analogous to c .

To quantify whether the observed temporal changes can be attributed to known and suspected mutational processes, we decomposed the mutational spectra at each time point into a catalogue of 57 mutational signatures, including double base substitution and indel signatures 24 (Methods).

In general, these mutational signatures display a predominantly undirected temporal variability over several orders of magnitude (Fig. 4c, d , Extended Data Fig. 7 ). In addition, several signatures demonstrate distinct temporal trends. As one may expect, signatures of exogenous mutagens are predominantly active in the early clonal stages of tumorigenesis. These include tobacco smoking in lung adenocarcinoma (signature SBS4, median fold change 0.43, IQR 0.31–0.72), consistent with previous reports 37 , 38 , and ultraviolet light exposure in melanoma (SBS7; median fold change 0.16, IQR 0.09–0.43). Another strong decrease over time is found for a signature of unknown aetiology, SBS12, which acts mostly in liver cancers (median fold change 0.22, IQR 0.06–0.41). In chronic lymphoid leukaemia, there was a 20-fold relative decrease in mutations associated with somatic hypermutation (SBS9; median fold change 0.05, IQR 0.02–0.43) from clonal to subclonal stages.

Some mutational processes tend to increase throughout cancer evolution. For example, we see that APOBEC mutagenesis (SBS2 and SBS13) increases in many cancer types from the early to late clonal stages (median fold change 2.0, IQR 0.8–3.6), as does a newly described signature SBS38 (median fold 3.6, IQR 1.8–11). Signatures of defective mismatch repair (SBS6, 14, 15, 20, 21, 26 and 44) increase from clonal to subclonal stages (median fold 1.8, IQR 1.2–3.0).

Chronological time estimates

The molecular timing data presented above do not measure the occurrence of events in chronological time. If the rate at which mutations are acquired per year in each sample was constant, the chronological time would simply be the product of the estimated molecular timing and age at diagnosis. However, this relation will be nonlinear if the mutation rate changes over time, and is inflated by acquired mutational processes, as suggested by the analysis in the previous section. Some of these issues can be mitigated by counting only mutations contributed by endogenous and less variable mutational processes, such as CpG-to-TpG mutations (hereafter CpG>TpG) caused by spontaneous deamination of 5-methyl-cytosine to thymine at CpG dinucleotides, which have been proposed as a molecular clock 12 . Our supplementary analysis suggests that, although the baseline CpG>TpG mutation rate in cancers is very close to that in normal cells, there appears to be a moderate increase (1–10 times, adding between 20 and 40% of mutations) in cancers (Extended Data Fig. 8 ). As this shifts chronological timing estimates, we model different scenarios of the evolution of the CpG>TpG mutation rate (Fig. 5a ).

figure 5

a , Mapping of molecular timing estimates to chronological time under different scenarios of increases in the CpG>TpG mutation rate. A greater increase before diagnosis indicates an inflation of the mutation timescale. b , Median latency between WGDs and the last detectable subclone before diagnosis under different scenarios of CpG>TpG mutation rate increases for n  = 569 non-hypermutant cancers with at least 100 informative SNVs, low tumour in normal contamination and at least five samples per tumour histology. c , Median latency between the MRCA and the last detectable subclone before diagnosis for different CpG>TpG mutation rate changes in n  = 1,921 non-hypermutant samples with low tumour in normal contamination and at least 5 cases per cancer type.

Applying this logic to time WGDs, which yield sufficient numbers of CpG>TpG mutations, demonstrates that they occur several years and possibly even a decade or more before diagnosis in some cancer types, under a range of scenarios of mutation rate increase (Fig. 5b , Extended Data Fig. 9 ). A notable example is ovarian adenocarcinoma, which appears to have a median latency of more than 10 years. This holds true even under a scenario of a CpG>TpG rate increase of 20-fold, which would be far beyond the 7.5-fold rate increase observed in matched primary and relapse samples 39 (Extended Data Fig. 8f ). Notably, these results suggest WGD may occur throughout the entire female reproductive life (Extended Data Fig. 9b ). The latency between the MRCA and the last detectable subclone is shorter, typically several months to years (Fig. 5c ).

These timescales of cancer evolution are further supported by the fact that progression of most known precancerous lesions to carcinomas usually spans many years, if not decades 40 , 41 , 42 , 43 , 44 , 45 . Our data corroborate these timescales and extend them to cancer types without detectable premalignant conditions, raising the hope that these tumours could also be detected in less malignant stages.

To our knowledge, our study presents the first large-scale genome-wide reconstruction of the evolutionary history of cancers, reconstructing both early (pre-cancer) and later stages of 38 cancer types. This is facilitated by the timing of copy number gains relative to all other events in the genome, through multiplicity and clonal status of co-amplified point mutations. However, several limitations exist ( Supplementary Information ). Perhaps most importantly, molecular timing is based on point mutations and is therefore subject to changes in mutation rate. Notably, healthy tissues acquire point mutations at rates not too dissimilar from those seen in cancers, particularly when considering only endogenous mutational processes, and furthermore, some tissues are riddled with microscopic clonal expansions of driver gene mutations 5 , 6 , 7 , 8 , 9 , 11 . This is direct evidence that the life history of almost every cell in the human body, including those that develop into cancer, is driven by somatic evolution.

Together, the data presented here enable us to draw approximate timelines summarizing the typical evolutionary history of each cancer type (Fig. 6 , Supplementary Information for all other cancer types). These make use of the qualitative timing of point mutations and copy number alterations, as well as signature activities, which can be interleaved with the chronological estimates of WGD and the appearance of the MRCA.

figure 6

a – d , Timelines representing the length of time, in years, between the fertilized egg and the median age of diagnosis for colorectal adenocarcinoma ( a ), squamous cell lung cancer ( b ), ovarian adenocarcinoma ( c ) and pancreatic adenocarcinoma ( d ). Real-time estimates for major events, such as WGD and the emergence of the MRCA, are used to define early, variable, late and subclonal stages of tumour evolution approximately in chronological time. The range of chronological time estimates according to varying clock mutation acceleration rates is shown as well, with tick marks corresponding to 1×, 2.5×, 5×, 7.5×, 10× and 20×. Driver mutations and copy number alterations (CNA) are shown in each stage according to their preferential timing, as defined by relative ordering. Mutational signatures (Sigs) that, on average, change over the course of tumour evolution, or are substantially active but not changing, are shown in the epoch in which their activity is greatest. DBS, double base substitution; SBS, single base substitutions. Where applicable, lesions with a known timing from the literature are annotated; dagger symbols denotes events that were found to have a different timing; asterisk symbol denotes events that agree with our timing.

It is remarkable that the evolution of practically all cancers displays some level of order, which agrees very well with, and adds much detail to, established models of cancer progression 35 , 46 . For example, TP53 with accompanying 17p deletion is one of the most frequent initiating mutations in a variety of cancers, including ovarian cancer, in which it is the hallmark of its precancerous precursor lesions 47 . Furthermore, the list of typically early drivers includes most other highly recurrent cancer genes, such as KRAS , TERT and CDKN2A , indicating a preferred role in early and possibly even pre-cancer evolution. This initially constrained set of genes broadens at later stages of cancer development, suggesting an epistatic fitness landscape canalizing the first steps of cancer evolution. Over time, as tumours evolve, they follow increasingly diverse paths driven by individually rare driver mutations, and by copy number alternations. However, none of these trends is absolute, and the evolutionary paths of individual tumours are highly variable, showing that cancer evolution follows trends, but is far from deterministic.

Our study sheds light on the typical timescales of in vivo tumour development, with initial driver events seemingly occurring up to decades before diagnosis, demonstrating how cancer genomes are shaped by a lifelong process of somatic evolution, with fluid boundaries between normal ageing processes 5 , 6 , 7 , 8 , 9 , 10 , 11 and cancer evolution. Nevertheless, the presence of genetic aberrations with such long latency raises hopes that aberrant clones could be detected early, before reaching their full malignant potential.

The PCAWG series consists of 2,778 tumour samples (2,703 white listed, 75 grey listed) from 2,658 donors. All samples in this dataset underwent whole-genome sequencing (minimum average coverage 30× in the tumour, 25× in the matched normal samples), and were processed with a set of project-specific pipelines for alignment, variant calling, and quality control 4 . Copy number calls were established by combining the output of six individual callers into a consensus using a multi-tier approach, resulting in a copy number profile, a purity and ploidy value and whether the tumour has undergone a WGD ( Supplementary Information ). Consensus subclonal architectures have been obtained by integrating the output of 11 subclonal reconstruction callers, after which all SNVs, indels and structural variants are assigned to a mutation cluster using the MutationTimer.R approach ( Supplementary Information ). Driver calls have been defined by the PCAWG Driver Working Group 4 , and mutational signatures are defined by the PCAWG Signatures Working Group 24 . A more detailed description can be found in  Supplementary Information, section 1 .

Data accrual was based on sequencing experiments performed by individual member groups of the ICGC and TCGA, as described in an associated study 4 . As this is a meta-analysis of existing data, power calculations were not performed and the investigators were not blinded to cancer diagnoses.

Timing of gains

We used three related approaches to calculate the timing of copy number gains (see  Supplementary Information, section 2 ). In brief, the common feature is that the expected VAF of a mutation ( E ) is related to the underlying number of alleles carrying a mutation according to the formula: E [ X ] =  nmfρ /[ N (1 −  ρ ) +  Cρ ], in which X is the number of reads, n denotes the coverage of the locus, the mutation copy number m is the number of alleles carrying the mutation (which is usually inferred), f is the frequency of the clone carrying the given mutation ( f  = 1 for clonal mutations). N is the normal copy number (2 on autosomes, 1 or 2 for chromosome X and 0 or 1 for chromosome Y), C is the total copy number of the tumour, and ρ is the purity of the sample.

The number of mutations n m  at each allelic copy number m  then informs about the time when the gain has occurred. The basic formulae for timing each gain are, depending on the copy number configuration:

in which 2 + 1 refers to major and minor copy number of 2 and 1, respectively. Methods differ slightly in how the number of mutations present on each allele are calculated and how uncertainty is handled ( Supplementary Information ).

Timing of mutations

The mutation copy number m and the clonal frequency f is calculated according to the principles indicated above. Details can be found in  Supplementary Information, section 2 . Mutations with f  = 1 are denoted as ‘clonal’, and mutations with f < 1 as ‘subclonal’. Mutations with f  = 1 and m > 1 are denoted as ‘early clonal’ (co-amplified). In cases with f  = 1, m  = 1 and C > 2, mutations were annotated as ‘late clonal’, if the minor copy number was 0, otherwise ‘clonal’ (unspecified).

Timing of driver mutations

A catalogue of driver point mutations (SNVs and indels) was provided by the PCAWG Drivers and Functional Interpretation Group 4 . The timing category was calculated as above. From the four timing categories, the odds ratios of early/late clonal and clonal (early, late or unspecified clonal)/subclonal were calculated for driver mutations against the distribution of all other mutations present in fragments with the same copy number composition in the samples with each particular driver. The background distribution of these odds ratios was assessed with 1,000 bootstraps ( Supplementary Information, section 4.1 ).

Integrative timing

For each pair of driver point mutations and recurrent copy number alterations, an ordering was established (earlier, later or unspecified). The information underlying this decision was derived from the timing of each driver point mutation, as well as from the timing status of clonal and subclonal copy number segments. These tables were aggregated across all samples and a sports statistics model was employed to calculate the overall ranking of driver mutations. A full description is given in  Supplementary Information, section 4.2 .

Mutational trinucleotide substitution signatures, as defined by the PCAWG Mutational Signatures Working Group 24 , were fit to samples with observed signature activity, after splitting point mutations into either of the four epochs. A likelihood ratio test based on the multinomial distribution was used to test for differences in the mutation spectra between time points. Time-resolved exposures were calculated using non-negative linear least squares. Full details are given in Supplementary Information, section 5 .

Real-time estimation of WGD and MRCA

CpG>TpG mutations were counted in an NpCpG context, except for skin–melanoma, in which CpCpG and TpCpG were excluded owing to the overlapping UV mutation spectrum. For visual comparison, the number of mutations was scaled to the effective genome size, defined as the 1/mean( m i / C i ), in which m i is the estimated number of allelic copies of each mutation, and C i is the total copy number at that locus, thereby scaling to the final copy number and the time of change.

A hierarchical Bayesian linear regression was fit to relate the age at diagnosis to the scaled number of mutations, ensuring positive slope and intercept through a shared gamma distribution across cancer types.

For tumours with several time points, the set of mutations shared between diagnosis and relapse ( n D ) and those specific to the relapse ( n R ) was calculated. The rate acceleration was calculated as: a  =  n R / n D  ×  t D / t R . This analysis was performed separately for all substitutions and for CpG>TpG mutations.

On the basis of these analyses, a typical increase of 5× for most cancer types was chosen, with a lower value of 2.5× for brain cancers and a value of 7.5× for ovarian cancer.

The correction for transforming an estimate of a copy number gain in mutation time into chronological time depends not only on the rate acceleration, but also on the time at which this acceleration occurred. As this is generally unknown, we performed Monte Carlo simulations of rate accelerations spanning an interval of 15 years before diagnosis, corresponding roughly to 25% of time for a diagnosis at 60 years of age, noting that a 5× rate increase over this duration yields an offset of about 33% of mutations, compatible with our data. Subclonal mutations were assumed to occur at full acceleration. The proportion of subclonal mutations was divided by the number of identified subclones, thus conservatively assuming branching evolution. Full details are given in  Supplementary Information, section 6 .

Cancer timelines

The results from each of the different timing analyses are combined in timelines of cancer evolution for each tumour type (Fig. 6 and Supplementary Information ). Each timeline begins at the fertilized egg, and spans up to the median age of diagnosis within each cohort. Real-time estimates for WGD and the MRCA act as anchor points, allowing us to roughly map the four broadly defined time periods (early clonal, intermediate, late clonal and subclonal) to chronological time during a patient’s lifespan. Specific driver mutations or copy number alterations can be placed within each of these time frames based on their ordering from the league model analysis. Signatures are shown if they typically change over time (95% confidence intervals of mean change not overlapping 0), and if they are strongly active (contributing at least 10% mutations to one time point). Signatures are shown on the timeline in the epoch of their greatest activity. Where an event found in our study has a known timing in the literature, the agreement is annotated on the timeline; with an asterisk denoting an agreed timing, and dagger symbol denoting a timing that is different to our results. Full details are given in  Supplementary Information, section 7 .

Reporting summary

Further information on research design is available in the  Nature Research Reporting Summary linked to this paper.

Data availability

Somatic and germline variant calls, mutational signatures, subclonal reconstructions, transcript abundance, splice calls and other core data generated by the ICGC/TCGA PCAWG Consortium are described elsewhere 4 and available for download at https://dcc.icgc.org/releases/PCAWG . Further information on accessing the data, including raw read files, can be found at https://docs.icgc.org/pcawg/data/ . In accordance with the data access policies of the ICGC and TCGA projects, most molecular, clinical and specimen data are in an open tier that does not require access approval. To access information that could potentially identify participants, such as germline alleles and underlying sequencing data, researchers will need to apply to the TCGA Data Access Committee (DAC) via dbGaP ( https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=login ) for access to the TCGA portion of the dataset, and to the ICGC Data Access Compliance Office (DACO; http://icgc.org/daco ) for the ICGC portion. In addition, to access somatic SNVs derived from TCGA donors, researchers will also need to obtain dbGaP authorization. Datasets used and results presented in this study, including timing estimates for copy number gains, chronological estimates of WGD and MRCA, as well as mutation signature changes, are described in  Supplementary Note 3 and are available at https://dcc.icgc.org/releases/PCAWG/evolution-heterogeneity .

Code availability

The core computational pipelines used by the PCAWG Consortium for alignment, quality control and variant calling are available to the public at https://dockstore.org/search?search=pcawg under the GNU General Public License v3.0, which allows for reuse and distribution. Analysis code presented in this study is available through the GitHub repository https://github.com/PCAWG-11/Evolution . This archive contains relevant software and analysis workflows as submodules, which include code for timing copy number gains, point mutations and mutation signatures, real-time timing and evolutionary league model analysis, as well as scripts to generate the figures presented: CancerTiming (v.3.1.8), MutationTimeR (v.0.1), PhylogicNDT (v.1.1) and a series of custom scripts (v. 1.0), with detailed versions of other packages used.

Change history

25 january 2023.

A Correction to this paper has been published: https://doi.org/10.1038/s41586-022-05601-4

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Acknowledgements

We thank H. Lee-Six and L. Moore for sharing data on mutation burden in normal tissues. This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001202), the UK Medical Research Council (FC001202) and the Wellcome Trust (FC001202). This project was enabled through the Crick Scientific Computing STP and through access to the MRC eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council (grant number MR/L016311/1). M.T. and J.D. are postdoctoral fellows supported by the European Union’s Horizon 2020 research and innovation program (Marie Skłodowska-Curie grant agreement number 747852-SIOMICS and 703594-DECODE). J.D. is a postdoctoral fellow of the FWO. F.M., G.M. and K. Yuan acknowledge the support of the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. G.M., K. Yuan and F.M. were funded by CRUK core grants C14303/A17197 and A19274. S. Sengupta and Y.J. are supported by NIH R01 CA132897. S.M. is supported by the Vanier Canada Graduate Scholarship. S.C.S. is supported by the NSERC Discovery Frontiers Project, “The Cancer Genome Collaboratory” and NIH Grant GM108308. H.Z. is supported by grant NIMH086633 and an endowed Bao-Shan Jing Professorship in Diagnostic Imaging. W.W. is supported by the US National Cancer Institute (1R01 CA183793 and P30 CA016672). P.T.S. was supported by U24CA210957 and 1U24CA143799. D.C.W. is funded by the Li Ka Shing foundation. P.V.L. is a Winton Group Leader in recognition of the Winton Charitable Foundation’s support towards the establishment of The Francis Crick Institute. We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonized variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.

Author information

These authors contributed equally: Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner, Stefan C. Dentro, Santiago Gonzalez

These authors jointly supervised this work: Paul T. Spellman, David C. Wedge, Peter Van Loo

A list of members and their affiliations appears at the end of the paper

A list of members and their affiliations appears online

Authors and Affiliations

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK

Moritz Gerstung, Santiago Gonzalez, Lara Jerman, Moritz Gerstung, Santiago Gonzalez & Lara Jerman

European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany

Moritz Gerstung & Moritz Gerstung

Wellcome Sanger Institute, Cambridge, UK

Moritz Gerstung, Stefan C. Dentro, Thomas J. Mitchell, Maxime Tarabichi, Ignacio Vázquez-García, Stefan C. Dentro, Moritz Gerstung, Maxime Tarabichi, David J. Adams, Peter J. Campbell, Kevin J. Dawson, Henry Lee-Six, Inigo Martincorena, Thomas J. Mitchell & Ignacio Vázquez-García

The Francis Crick Institute, London, UK

Clemency Jolly, Stefan C. Dentro, Maxime Tarabichi, Kerstin Haase, Jonas Demeulemeester, Stefan C. Dentro, Clemency Jolly, Kerstin Haase, Maxime Tarabichi, Jonas Demeulemeester, Matthew Fittall, Peter Van Loo & Peter Van Loo

Broad Institute of MIT and Harvard, Cambridge, MA, USA

Ignaty Leshchiner, Daniel Rosebrock, Dimitri G. Livitz, Steven Schumacher, Gad Getz, Rameen Beroukhim, Ignaty Leshchiner, Rameen Beroukhim, Gad Getz, Gavin Ha, Dimitri G. Livitz, Daniel Rosebrock, Steven Schumacher & Oliver Spiro

Big Data Institute, University of Oxford, Oxford, UK

Stefan C. Dentro, Stefan C. Dentro, David C. Wedge & David C. Wedge

University of Cambridge, Cambridge, UK

Thomas J. Mitchell, Ignacio Vázquez-García, Thomas J. Mitchell & Ignacio Vázquez-García

University of Toronto, Toronto, Ontario, Canada

Yulia Rubanova, Amit Deshwar, Jeff Wintersinger, Paul C. Boutros, Quaid D. Morris, Jeff Wintersinger, Amit G. Deshwar, Yulia Rubanova, Paul C. Boutros, Ruian Shi, Shankar Vembu & Quaid D. Morris

Vector Institute, Toronto, Ontario, Canada

Yulia Rubanova, Amit Deshwar, Jeff Wintersinger, Quaid D. Morris, Jeff Wintersinger, Amit G. Deshwar, Yulia Rubanova & Quaid D. Morris

Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA

Pavana Anur, Pavana Anur, Myron Peto, Paul T. Spellman & Paul T. Spellman

The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Kaixian Yu, Yu Fan, Hongtu Zhu, Wenyi Wang, Kaixian Yu, Shaolong Cao, Yu Fan, Seung Jun Shin, Hongtu Zhu & Wenyi Wang

German Cancer Research Center (DKFZ), Heidelberg, Germany

Kortine Kleinheinz, Matthias Schlesner, Roland Eils, Kortine Kleinheinz & Matthias Schlesner

Heidelberg University, Heidelberg, Germany

Kortine Kleinheinz, Roland Eils & Kortine Kleinheinz

University of Ljubljana, Ljubljana, Slovenia

Lara Jerman & Lara Jerman

NorthShore University HealthSystem, Evanston, IL, USA

Subhajit Sengupta, Yuan Ji, Yuan Ji & Subhajit Sengupta

Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK

Geoff Macintyre, Florian Markowetz, Ke Yuan, Geoff Macintyre, Ruben M. Drews, Florian Markowetz & Ke Yuan

Simon Fraser University, Burnaby, British Columbia, Canada

Salem Malikic, Nilgun Donmez, Nilgun Donmez & Salem Malikic

Vancouver Prostate Centre, Vancouver, British Columbia, Canada

Salem Malikic, Nilgun Donmez, S. Cenk Sahinalp, Nilgun Donmez, Salem Malikic & S. Cenk Sahinalp

University of Melbourne, Melbourne, Victoria, Australia

Marek Cmero, Elizabeth L. Christie, Marek Cmero & Dale W. Garsed

Walter and Eliza Hall Institute, Melbourne, Victoria, Australia

Marek Cmero & Marek Cmero

University of Leuven, Leuven, Belgium

Jonas Demeulemeester, Jonas Demeulemeester, Peter Van Loo & Peter Van Loo

Weill Cornell Medicine, New York, NY, USA

Xiaotong Yao, Marcin Imielinski, Marcin Imielinski & Xiaotong Yao

New York Genome Center, New York, NY, USA

University of California Santa Cruz, Santa Cruz, CA, USA

Juhee Lee & Juhee Lee

Ontario Institute for Cancer Research, Toronto, Ontario, Canada

Paul C. Boutros, Paul C. Boutros, Adriana Salcedo & Lincoln D. Stein

University of California, Los Angeles, CA, USA

Paul C. Boutros & Paul C. Boutros

Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

Harvard Medical School, Boston, MA, USA

Dana-Farber Cancer Institute, Boston, MA, USA

Rameen Beroukhim & Rameen Beroukhim

Indiana University, Bloomington, IN, USA

S. Cenk Sahinalp & S. Cenk Sahinalp

The University of Chicago, Chicago, IL, USA

Yuan Ji & Yuan Ji

University of Cologne, Cologne, Germany

Martin Peifer, Yupeng Cun, Martin Peifer & Tsun-Po Yang

University of Helsinki, Helsinki, Finland

Ville Mustonen & Ville Mustonen

University of Glasgow, Glasgow, UK

Ke Yuan & Ke Yuan

Oxford NIHR Biomedical Research Centre, Oxford, UK

David C. Wedge & David C. Wedge

Department of Computer Science, Carleton College, Northfield, MN, USA

Layla Oesper

Department of Computer Science, Princeton University, Princeton, NJ, USA

Benjamin J. Raphael

Korea University, Seoul, South Korea

Seung Jun Shin

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

David A. Wheeler

Applied Tumor Genomics Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland

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Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK

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Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, School of Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea

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Department of Oncology, Gil Medical Center, Gachon University, Incheon, South Korea

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Hiroshima University, Hiroshima, Japan

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Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany

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UC San Diego Moores Cancer Center, San Diego, CA, USA

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Royal National Orthopaedic Hospital - Bolsover, London, UK

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Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Quantitative and Computational Biosciences Graduate Program, Baylor College of Medicine, Houston, TX, USA

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Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany

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Salford Royal NHS Foundation Trust, Salford, UK

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Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy

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Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada

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The McDonnell Genome Institute at Washington University, St. Louis, MO, USA

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University College London, London, UK

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DLR Project Management Agency, Bonn, Germany

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Los Alamos National Laboratory, Los Alamos, NM, USA

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Department of Pathology, University Health Network, Toronto General Hospital, Toronto, ON, Canada

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Nottingham University Hospitals NHS Trust, Nottingham, UK

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Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

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Vector Institute, Toronto, ON, Canada

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Hematopathology Section, Institute of Pathology, Christian-Albrechts-University, Kiel, Germany

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Pathology, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

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Department of Veterinary Medicine, Transmissible Cancer Group, University of Cambridge, Cambridge, UK

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Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

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Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK

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Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

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Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, USA

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Department of Pediatrics, Harvard Medical School, Boston, MA, USA

Leeds Institute of Medical Research @ St. James’s, University of Leeds, St. James’s University Hospital, Leeds, UK

Rosamonde E. Banks & Naveen Vasudev

Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy

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Department of Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia

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Genome Canada, Ottawa, ON, Canada

CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

Sergi Beltran, Ivo G. Gut, Marta Gut, Simon C. Heath, Tomas Marques-Bonet, Arcadi Navarro, Miranda D. Stobbe, Jean-Rémi Trotta & Justin P. Whalley

Universitat Pompeu Fabra (UPF), Barcelona, Spain

Sergi Beltran, Mattia Bosio, German M. Demidov, Oliver Drechsel, Ivo G. Gut, Marta Gut, Simon C. Heath, Francesc Muyas, Stephan Ossowski, Aparna Prasad, Raquel Rabionet, Miranda D. Stobbe & Hana Susak

Buck Institute for Research on Aging, Novato, CA, USA

Christopher Benz & Christina Yau

Duke University Medical Center, Durham, NC, USA

Andrew Berchuck

Department of Human Genetics, Hannover Medical School, Hannover, Germany

Anke K. Bergmann

Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Benjamin P. Berman & Huy Q. Dinh

Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Benjamin P. Berman

The Hebrew University Faculty of Medicine, Jerusalem, Israel

Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Daniel M. Berney & Yong-Jie Lu

Department of Computer Science, Bioinformatics Group, University of Leipzig, Leipzig, Germany

Stephan H. Bernhart, Hans Binder, Steve Hoffmann & Peter F. Stadler

Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany

Stephan H. Bernhart, Hans Binder, Steve Hoffmann, Helene Kretzmer & Peter F. Stadler

Transcriptome Bioinformatics, LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany

Stephan H. Bernhart, Steve Hoffmann, Helene Kretzmer & Peter F. Stadler

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Rameen Beroukhim, Angela N. Brooks, Susan Bullman, Andrew D. Cherniack, Levi Garraway, Matthew Meyerson, Chandra Sekhar Pedamallu, Steven E. Schumacher, Juliann Shih & Jeremiah A. Wala

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA

Rameen Beroukhim, Aquila Fatima, Andrea L. Richardson, Steven E. Schumacher, Ofer Shapira, Andrew Tutt & Jeremiah A. Wala

Rameen Beroukhim, Gad Getz, Kirsten Kübler, Matthew Meyerson, Chandra Sekhar Pedamallu, Paz Polak, Esther Rheinbay & Jeremiah A. Wala

USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

Mario Berrios, Moiz S. Bootwalla, Andrea Holbrook, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg & Daniel J. Weisenberger

Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy

Samantha Bersani, Ivana Cataldo, Claudio Luchini & Maria Scardoni

Department of Mathematics, Aarhus University, Aarhus, Denmark

Johanna Bertl & Asger Hobolth

Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus N, Denmark

Johanna Bertl, Henrik Hornshøj, Malene Juul, Randi Istrup Juul, Tobias Madsen, Morten Muhlig Nielsen & Jakob Skou Pedersen

Instituto Carlos Slim de la Salud, Mexico City, Mexico

Miguel Betancourt

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Vinayak Bhandari, Paul C. Boutros, Robert G. Bristow, Keren Isaev, Constance H. Li, Jüri Reimand, Michael H. A. Roehrl & Bradly G. Wouters

Cancer Division, Garvan Institute of Medical Research, Kinghorn Cancer Centre, University of New South Wales (UNSW Sydney), Sydney, NSW, Australia

Andrew V. Biankin, David K. Chang, Lorraine A. Chantrill, Angela Chou, Anthony J. Gill, Amber L. Johns, James G. Kench, David K. Miller, Adnan M. Nagrial, Marina Pajic, Mark Pinese, Ilse Rooman, Christopher J. Scarlett, Christopher W. Toon & Jianmin Wu

South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales (UNSW Sydney), Liverpool, NSW, Australia

Andrew V. Biankin

West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK

Andrew V. Biankin & Nigel B. Jamieson

Center for Digital Health, Berlin Institute of Health and Charitè - Universitätsmedizin Berlin, Berlin, Germany

Matthias Bieg

Heidelberg Center for Personalized Oncology (DKFZ-HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany

Matthias Bieg, Ivo Buchhalter, Barbara Hutter & Nagarajan Paramasivam

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

Darell Bigner

Massachusetts General Hospital, Boston, MA, USA

Michael Birrer, Vikram Deshpande, William C. Faquin, Nicholas J. Haradhvala, Kirsten Kübler, Michael S. Lawrence, David N. Louis, Yosef E. Maruvka, G. Petur Nielsen, Esther Rheinbay, Mara Rosenberg, Dennis C. Sgroi & Chin-Lee Wu

National Institute of Biomedical Genomics, Kalyani, West Bengal, India

Nidhan K. Biswas, Arindam Maitra & Partha P. Majumder

Institute of Clinical Medicine and Institute of Oral Biology, University of Oslo, Oslo, Norway

Bodil Bjerkehagen

University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Lori Boice, Mei Huang, Sonia Puig & Leigh B. Thorne

ARC-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy

Giada Bonizzato, Cinzia Cantù, Ivana Cataldo, Vincenzo Corbo, Sonia Grimaldi, Rita T. Lawlor, Andrea Mafficini, Borislav C. Rusev, Aldo Scarpa, Katarzyna O. Sikora, Nicola Sperandio, Alain Viari & Caterina Vicentini

The Institute of Cancer Research, London, UK

Johann S. De Bono, Niedzica Camacho, Colin S. Cooper, Sandra E. Edwards, Rosalind A. Eeles, Zsofia Kote-Jarai, Daniel A. Leongamornlert, Lucy Matthews & Sue Merson

Centre for Computational Biology, Duke-NUS Medical School, Singapore, Singapore

Arnoud Boot, Ioana Cutcutache, Mi Ni Huang, John R. McPherson, Steven G. Rozen & Yang Wu

Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore

Arnoud Boot, Ioana Cutcutache, Mi Ni Huang, John R. McPherson, Steven G. Rozen, Patrick Tan, Bin Tean Teh & Yang Wu

Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden

Ake Borg, Markus Ringnér & Johan Staaf

Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany

Arndt Borkhardt & Jessica I. Hoell

Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Keith A. Boroevich, Todd A. Johnson, Michael S. Lawrence & Tatsuhiko Tsunoda

RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

Keith A. Boroevich, Akihiro Fujimoto, Masashi Fujita, Mayuko Furuta, Kazuhiro Maejima, Hidewaki Nakagawa, Kaoru Nakano & Aya Sasaki-Oku

Department of Internal Medicine/Hematology, Friedrich-Ebert-Hospital, Neumünster, Germany

Christoph Borst & Siegfried Haas

Departments of Dermatology and Pathology, Yale University, New Haven, CT, USA

Marcus Bosenberg

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

Mattia Bosio, German M. Demidov, Oliver Drechsel, Georgia Escaramis, Xavier Estivill, Aliaksei Z. Holik, Francesc Muyas, Stephan Ossowski, Raquel Rabionet & Hana Susak

Radcliffe Department of Medicine, University of Oxford, Oxford, UK

Jacqueline Boultwood

Canadian Center for Computational Genomics, McGill University, Montreal, QC, Canada

Guillaume Bourque

Department of Human Genetics, McGill University, Montreal, QC, Canada

Guillaume Bourque, Mark Lathrop & Yasser Riazalhosseini

Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA

Paul C. Boutros

Department of Pharmacology, University of Toronto, Toronto, ON, Canada

Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland

G. Steven Bova & Tapio Visakorpi

Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK

David T. Bowen

Translational Research and Innovation, Centre Léon Bérard, Lyon, France

Sandrine Boyault

Fox Chase Cancer Center, Philadelphia, PA, USA

Jeffrey Boyd & Elaine R. Mardis

International Agency for Research on Cancer, World Health Organization, Lyon, France

Paul Brennan & Ghislaine Scelo

Earlham Institute, Norwich, UK

Daniel S. Brewer & Colin S. Cooper

Norwich Medical School, University of East Anglia, Norwich, UK

Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, HB, The Netherlands

Arie B. Brinkman

CRUK Manchester Institute and Centre, Manchester, UK

Robert G. Bristow

Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada

Division of Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Manchester, UK

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada

Robert G. Bristow & Fei-Fei Fei Liu

Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Jane E. Brock & Sabina Signoretti

Department of Surgery, Division of Thoracic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Malcolm Brock

Division of Molecular Pathology, The Netherlands Cancer Institute, Oncode Institute, Amsterdam, CX, The Netherlands

Annegien Broeks & Jos Jonkers

Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA

Angela N. Brooks, David Haan, Maximillian G. Marin, Thomas J. Matthew, Yulia Newton, Cameron M. Soulette & Joshua M. Stuart

UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA

Angela N. Brooks, Brian Craft, Mary J. Goldman, David Haussler, Joshua M. Stuart & Jingchun Zhu

Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Benedikt Brors, Lars Feuerbach, Chen Hong, Charles David Imbusch & Lina Sieverling

German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

Benedikt Brors, Barbara Hutter, Peter Lichter, Dirk Schadendorf & Holger Sültmann

National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany

Benedikt Brors, Barbara Hutter, Holger Sültmann & Thorsten Zenz

Center for Biological Sequence Analysis, Department of Bio and Health Informatics, Technical University of Denmark, Lyngby, Denmark

Søren Brunak

Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark

Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD, Australia

Timothy J. C. Bruxner, Oliver Holmes, Stephen H. Kazakoff, Conrad R. Leonard, Felicity Newell, Katia Nones, Ann-Marie Patch, John V. Pearson, Michael C. Quinn, Nick M. Waddell, Nicola Waddell, Scott Wood & Qinying Xu

Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA

Alex Buchanan & Kyle Ellrott

Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Ivo Buchhalter, Calvin Wing Yiu Chan, Roland Eils, Michael C. Heinold, Carl Herrmann, Natalie Jäger, Rolf Kabbe, Jules N. A. Kerssemakers, Kortine Kleinheinz, Nagarajan Paramasivam, Manuel Prinz, Matthias Schlesner & Johannes Werner

Institute of Pharmacy and Molecular Biotechnology and BioQuant, Heidelberg University, Heidelberg, Germany

Ivo Buchhalter, Roland Eils, Michael C. Heinold, Carl Herrmann, Daniel Hübschmann, Kortine Kleinheinz & Umut H. Toprak

Federal Ministry of Education and Research, Berlin, Germany

Christiane Buchholz

Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia

Hazel Burke, Ricardo De Paoli-Iseppi, Nicholas K. Hayward, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Georgina V. Long, Graham J. Mann, Robyn P. M. Saw, Richard A. Scolyer, Ping Shang, Andrew J. Spillane, Jonathan R. Stretch, John F. F. Thompson & James S. Wilmott

Pediatric Hematology and Oncology, University Hospital Muenster, Muenster, Germany

Birgit Burkhardt

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Kathleen H. Burns & Christopher Umbricht

McKusick-Nathans Institute of Genetic Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD, USA

Kathleen H. Burns

Foundation Medicine, Inc, Cambridge, MA, USA

John Busanovich

Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA

Carlos D. Bustamante & Francisco M. De La Vega

Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

Carlos D. Bustamante, Francisco M. De La Vega, Suyash S. Shringarpure, Nasa Sinnott-Armstrong & Mark H. Wright

Bakar Computational Health Sciences Institute and Department of Pediatrics, University of California, San Francisco, CA, USA

Atul J. Butte & Jieming Chen

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

Anne-Lise Børresen-Dale

National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen & Jiashan Zhang

Royal Marsden NHS Foundation Trust, London and Sutton, UK

Declan Cahill, Nening M. Dennis, Tim Dudderidge, Rosalind A. Eeles, Cyril Fisher, Steven Hazell, Vincent Khoo, Pardeep Kumar, Naomi Livni, Erik Mayer, David Nicol, Christopher Ogden, Edward W. Rowe, Sarah Thomas, Alan Thompson & Nicholas van As

Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

Claudia Calabrese, Serap Erkek, Moritz Gerstung, Santiago Gonzalez, Nina Habermann, Wolfgang Huber, Lara Jerman, Jan O. Korbel, Esa Pitkänen, Benjamin Raeder, Tobias Rausch, Vasilisa A. Rudneva, Oliver Stegle, Stephanie Sungalee, Lara Urban, Sebastian M. Waszak, Joachim Weischenfeldt & Sergei Yakneen

Department of Oncology, University of Cambridge, Cambridge, UK

Carlos Caldas & Suet-Feung Chin

Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK

Carlos Caldas, Suet-Feung Chin, Ruben M. Drews, Paul A. Edwards, Matthew Eldridge, Steve Hawkins, Andy G. Lynch, Geoff Macintyre, Florian Markowetz, Charlie E. Massie, David E. Neal, Simon Tavaré & Ke Yuan

Institut Gustave Roussy, Villejuif, France

Fabien Calvo

Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Peter J. Campbell, Vincent J. Gnanapragasam, William Howat, Thomas J. Mitchell, David E. Neal, Nimish C. Shah & Anne Y. Warren

Department of Haematology, University of Cambridge, Cambridge, UK

Peter J. Campbell

Anatomia Patológica, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

Elias Campo

Spanish Ministry of Science and Innovation, Madrid, Spain

University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

Thomas E. Carey

Department for BioMedical Research, University of Bern, Bern, Switzerland

Joana Carlevaro-Fita

Department of Medical Oncology, Inselspital, University Hospital and University of Bern, Bern, Switzerland

Joana Carlevaro-Fita, Rory Johnson & Andrés Lanzós

Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland

Joana Carlevaro-Fita & Andrés Lanzós

University of Pavia, Pavia, Italy

Mario Cazzola & Luca Malcovati

University of Alabama at Birmingham, Birmingham, AL, USA

Robert Cerfolio

UHN Program in BioSpecimen Sciences, Toronto General Hospital, Toronto, ON, Canada

Dianne E. Chadwick, Sheng-Ben Liang, Michael H. A. Roehrl & Sagedeh Shahabi

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Dimple Chakravarty

Centre for Law and Genetics, University of Tasmania, Sandy Bay Campus, Hobart, TAS, Australia

Don Chalmers

Faculty of Biosciences, Heidelberg University, Heidelberg, Germany

Calvin Wing Yiu Chan, Chen Hong & Lina Sieverling

Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA

Vishal S. Chandan

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Stephen J. Chanock, Xing Hua, Lisa Mirabello, Lei Song & Bin Zhu

Illawarra Shoalhaven Local Health District L3 Illawarra Cancer Care Centre, Wollongong Hospital, Wollongong, NSW, Australia

Lorraine A. Chantrill

BioForA, French National Institute for Agriculture, Food, and Environment (INRAE), ONF, Orléans, France

Aurélien Chateigner

Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

Nilanjan Chatterjee

University of California San Diego, San Diego, CA, USA

Zhaohong Chen, Michelle T. Dow, Claudiu Farcas, S. M. Ashiqul Islam, Antonios Koures, Lucila Ohno-Machado, Christos Sotiriou & Ashley Williams

Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA

Jeremy Chien

Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia

Yoke-Eng Chiew, Angela Chou, Jillian A. Hung, Catherine J. Kennedy, Graham J. Mann, Gulietta M. Pupo, Sarah-Jane Schramm, Varsha Tembe & Anna deFazio

Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia

Yoke-Eng Chiew, Jillian A. Hung, Catherine J. Kennedy & Anna deFazio

PDXen Biosystems Inc, Seoul, South Korea

Sunghoon Cho

Korea Advanced Institute of Science and Technology, Daejeon, South Korea

Jung Kyoon Choi, Young Seok Ju & Christopher J. Yoon

Electronics and Telecommunications Research Institute, Daejeon, South Korea

Wan Choi, Seung-Hyup Jeon, Hyunghwan Kim & Youngchoon Woo

Institut National du Cancer (INCA), Boulogne-Billancourt, France

Christine Chomienne & Iris Pauporté

Department of Genetics, Informatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA

Zechen Chong

Division of Medical Oncology, National Cancer Centre, Singapore, Singapore

Su Pin Choo

Medical Oncology, University and Hospital Trust of Verona, Verona, Italy

Sara Cingarlini & Michele Milella

Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany

Alexander Claviez

Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON, Canada

Sean Cleary, Ashton A. Connor & Steven Gallinger

School of Biological Sciences, University of Auckland, Auckland, New Zealand

Nicole Cloonan

Department of Surgery, University of Melbourne, Parkville, VIC, Australia

Marek Cmero

The Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia

Walter and Eliza Hall Institute, Parkville, VIC, Australia

Vancouver Prostate Centre, Vancouver, Canada

Colin C. Collins, Nilgun Donmez, Faraz Hach, Salem Malikic, S. Cenk Sahinalp, Iman Sarrafi & Raunak Shrestha

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

Ashton A. Connor, Steven Gallinger, Robert C. Grant, Treasa A. McPherson & Iris Selander

University of East Anglia, Norwich, UK

Colin S. Cooper

Norfolk and Norwich University Hospital NHS Trust, Norwich, UK

Matthew G. Cordes, Catrina C. Fronick & Tom Roques

Victorian Institute of Forensic Medicine, Southbank, VIC, Australia

Stephen M. Cordner

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA

Isidro Cortés-Ciriano, Jake June-Koo Lee & Peter J. Park

Department of Chemistry, Centre for Molecular Science Informatics, University of Cambridge, Cambridge, UK

Isidro Cortés-Ciriano

Ludwig Center at Harvard Medical School, Boston, MA, USA

Kyle Covington, HarshaVardhan Doddapaneni, Richard A. Gibbs, Jianhong Hu, Joy C. Jayaseelan, Viktoriya Korchina, Lora Lewis, Donna M. Muzny, Linghua Wang, David A. Wheeler & Liu Xi

Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia

Prue A. Cowin, Anne Hamilton, Gisela Mir Arnau & Ravikiran Vedururu

Physics Division, Optimization and Systems Biology Lab, Massachusetts General Hospital, Boston, MA, USA

David Craft

Department of Medicine, Baylor College of Medicine, Houston, TX, USA

Chad J. Creighton

Yupeng Cun, Martin Peifer & Tsun-Po Yang

International Genomics Consortium, Phoenix, AZ, USA

Erin Curley & Troy Shelton

Genomics Research Program, Ontario Institute for Cancer Research, Toronto, ON, Canada

Karolina Czajka, Jenna Eagles, Thomas J. Hudson, Jeremy Johns, Faridah Mbabaali, John D. McPherson, Jessica K. Miller, Danielle Pasternack, Michelle Sam & Lee E. Timms

Barking Havering and Redbridge University Hospitals NHS Trust, Romford, UK

Bogdan Czerniak, Adel El-Naggar & David Khoo

Children’s Hospital at Westmead, University of Sydney, Sydney, NSW, Australia

Rebecca A. Dagg

Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, Verona, Italy

Maria Vittoria Davi

Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Natalie R. Davidson, Andre Kahles, Kjong-Van Lehmann, Alessandro Pastore, Gunnar Rätsch, Chris Sander, Yasin Senbabaoglu & Nicholas D. Socci

Department of Biology, ETH Zurich, Zürich, Switzerland

Natalie R. Davidson, Andre Kahles, Kjong-Van Lehmann, Gunnar Rätsch & Stefan G. Stark

Department of Computer Science, ETH Zurich, Zurich, Switzerland

Natalie R. Davidson, Andre Kahles, Kjong-Van Lehmann & Gunnar Rätsch

SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland

Weill Cornell Medical College, New York, NY, USA

Natalie R. Davidson, Bishoy M. Faltas & Gunnar Rätsch

Academic Department of Medical Genetics, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

Helen Davies & Serena Nik-Zainal

MRC Cancer Unit, University of Cambridge, Cambridge, UK

Helen Davies, Rebecca C. Fitzgerald, Nicola Grehan, Serena Nik-Zainal & Maria O’Donovan

Departments of Pediatrics and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Ian J. Davis

Seven Bridges Genomics, Charlestown, MA, USA

Brandi N. Davis-Dusenbery, Sinisa Ivkovic, Milena Kovacevic, Ana Mijalkovic Lazic, Sanja Mijalkovic, Mia Nastic, Petar Radovic & Nebojsa Tijanic

Annai Systems, Inc, Carlsbad, CA, USA

Francisco M. De La Vega, Tal Shmaya & Dai-Ying Wu

Department of Pathology, General Hospital of Treviso, Department of Medicine, University of Padua, Treviso, Italy

Angelo P. Dei Tos

Department of Computational Biology, University of Lausanne, Lausanne, Switzerland

Olivier Delaneau

Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, CH, Switzerland

Swiss Institute of Bioinformatics, University of Geneva, Geneva, CH, Switzerland

Jonas Demeulemeester, Stefan C. Dentro, Matthew W. Fittall, Kerstin Haase, Clemency Jolly, Maxime Tarabichi & Peter Van Loo

Jonas Demeulemeester & Peter Van Loo

Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany

German M. Demidov, Francesc Muyas & Stephan Ossowski

Computational and Systems Biology, Genome Institute of Singapore, Singapore, Singapore

Deniz Demircioğlu & Jonathan Göke

School of Computing, National University of Singapore, Singapore, Singapore

Deniz Demircioğlu

Big Data Institute, Li Ka Shing Centre, University of Oxford, Oxford, UK

Stefan C. Dentro & David C. Wedge

Biomedical Data Science Laboratory, Francis Crick Institute, London, UK

Nikita Desai

Bioinformatics Group, Department of Computer Science, University College London, London, UK

The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada

Amit G. Deshwar

Breast Cancer Translational Research Laboratory JC Heuson, Institut Jules Bordet, Brussels, Belgium

Christine Desmedt

Department of Oncology, Laboratory for Translational Breast Cancer Research, KU Leuven, Leuven, Belgium

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain

Jordi Deu-Pons, Joan Frigola, Abel Gonzalez-Perez, Ferran Muiños, Loris Mularoni, Oriol Pich, Iker Reyes-Salazar, Carlota Rubio-Perez, Radhakrishnan Sabarinathan & David Tamborero

Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain

Jordi Deu-Pons, Abel Gonzalez-Perez, Ferran Muiños, Loris Mularoni, Oriol Pich, Carlota Rubio-Perez, Radhakrishnan Sabarinathan & David Tamborero

Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada

Neesha C. Dhani, David Hedley & Malcolm J. Moore

Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA

Priyanka Dhingra, Ekta Khurana, Eric Minwei Liu & Alexander Martinez-Fundichely

Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA

Department of Pathology, UPMC Shadyside, Pittsburgh, PA, USA

Independent Consultant, Wellesley, USA

Anthony DiBiase

Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

Klev Diamanti, Jan Komorowski & Husen M. Umer

Department of Medicine and Department of Genetics, Washington University School of Medicine, St. Louis, St. Louis, MO, USA

Li Ding, Robert S. Fulton, Michael D. McLellan, Michael C. Wendl & Venkata D. Yellapantula

Hefei University of Technology, Anhui, China

Shuai Ding & Shanlin Yang

Translational Cancer Research Unit, GZA Hospitals St.-Augustinus, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium

Luc Dirix, Steven Van Laere, Gert G. Van den Eynden & Peter Vermeulen

Simon Fraser University, Burnaby, BC, Canada

Nilgun Donmez, Ermin Hodzic, Salem Malikic, S. Cenk Sahinalp & Iman Sarrafi

University of Pennsylvania, Philadelphia, PA, USA

Ronny Drapkin

Faculty of Science and Technology, University of Vic—Central University of Catalonia (UVic-UCC), Vic, Spain

Ana Dueso-Barroso

The Wellcome Trust, London, UK

Michael Dunn

The Hospital for Sick Children, Toronto, ON, Canada

Lewis Jonathan Dursi

Department of Pathology, Queen Elizabeth University Hospital, Glasgow, UK

Fraser R. Duthie

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

Ken Dutton-Regester, Nicholas K. Hayward, Oliver Holmes, Peter A. Johansson, Stephen H. Kazakoff, Conrad R. Leonard, Felicity Newell, Katia Nones, Ann-Marie Patch, John V. Pearson, Antonia L. Pritchard, Michael C. Quinn, Paresh Vyas, Nicola Waddell, Scott Wood & Qinying Xu

Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK

Douglas F. Easton

Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK

Prostate Cancer Canada, Toronto, ON, Canada

Stuart Edmonds

Paul A. Edwards, Anthony R. Green, Andy G. Lynch, Florian Markowetz & Thomas J. Mitchell

Department of Laboratory Medicine, Translational Cancer Research, Lund University Cancer Center at Medicon Village, Lund University, Lund, Sweden

Anna Ehinger

Juergen Eils, Roland Eils & Daniel Hübschmann

New BIH Digital Health Center, Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin, Berlin, Germany

Juergen Eils, Roland Eils & Chris Lawerenz

CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Georgia Escaramis

Research Group on Statistics, Econometrics and Health (GRECS), UdG, Barcelona, Spain

Quantitative Genomics Laboratories (qGenomics), Barcelona, Spain

Xavier Estivill

Icelandic Cancer Registry, Icelandic Cancer Society, Reykjavik, Iceland

Jorunn E. Eyfjord, Holmfridur Hilmarsdottir & Jon G. Jonasson

State Key Laboratory of Cancer Biology, and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Shaanxi, China

Daiming Fan & Yongzhan Nie

Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy

Matteo Fassan

Rigshospitalet, Copenhagen, Denmark

Francesco Favero

Center for Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Martin L. Ferguson

Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC, Canada

Vincent Ferretti

Australian Institute of Tropical Health and Medicine, James Cook University, Douglas, QLD, Australia

Matthew A. Field

Department of Neuro-Oncology, Istituto Neurologico Besta, Milano, Italy

Gaetano Finocchiaro

Bioplatforms Australia, North Ryde, NSW, Australia

Anna Fitzgerald & Catherine A. Shang

Department of Pathology (Research), University College London Cancer Institute, London, UK

Adrienne M. Flanagan

Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada

Neil E. Fleshner

Department of Medical Oncology, Josephine Nefkens Institute and Cancer Genomics Centre, Erasmus Medical Center, Rotterdam, CN, The Netherlands

John A. Foekens, John W. M. Martens, F. Germán Rodríguez-González, Anieta M. Sieuwerts & Marcel Smid

The University of Queensland Thoracic Research Centre, The Prince Charles Hospital, Brisbane, QLD, Australia

Kwun M. Fong

CIBIO/InBIO - Research Center in Biodiversity and Genetic Resources, Universidade do Porto, Vairão, Portugal

Nuno A. Fonseca

HCA Laboratories, London, UK

Christopher S. Foster

University of Liverpool, Liverpool, UK

The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel

Milana Frenkel-Morgenstern

Department of Neurosurgery, University of Florida, Gainesville, FL, USA

William Friedman

Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Masashi Fukayama & Tetsuo Ushiku

University of Milano Bicocca, Monza, Italy

Carlo Gambacorti-Passerini

BGI-Shenzhen, Shenzhen, China

Shengjie Gao, Yong Hou, Chang Li, Lin Li, Siliang Li, Xiaobo Li, Xinyue Li, Dongbing Liu, Xingmin Liu, Qiang Pan-Hammarström, Hong Su, Jian Wang, Kui Wu, Heng Xiong, Huanming Yang, Chen Ye, Xiuqing Zhang, Yong Zhou & Shida Zhu

Department of Pathology, Oslo University Hospital Ulleval, Oslo, Norway

Øystein Garred

Center for Biomedical Informatics, Harvard Medical School, Boston, MA, USA

Nils Gehlenborg

Department Biochemistry and Molecular Biomedicine, University of Barcelona, Barcelona, Spain

Josep L. L. Gelpi

Office of Cancer Genomics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Daniela S. Gerhard

Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Clarissa Gerhauser, Christoph Plass & Dieter Weichenhan

Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Jeffrey E. Gershenwald

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Department of Computer Science, Yale University, New Haven, CT, USA

Mark Gerstein & Fabio C. P. Navarro

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA

Mark Gerstein, Sushant Kumar, Lucas Lochovsky, Shaoke Lou, Patrick D. McGillivray, Fabio C. P. Navarro, Leonidas Salichos & Jonathan Warrell

Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA

Mark Gerstein, Arif O. Harmanci, Sushant Kumar, Donghoon Lee, Shantao Li, Xiaotong Li, Lucas Lochovsky, Shaoke Lou, William Meyerson, Leonidas Salichos, Jonathan Warrell, Jing Zhang & Yan Zhang

Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA

Gad Getz & Paz Polak

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ronald Ghossein, Dilip D. Giri, Christine A. Iacobuzio-Donahue, Jorge Reis-Filho & Victor Reuter

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

Nasra H. Giama, Catherine D. Moser & Lewis R. Roberts

University of Sydney, Sydney, NSW, Australia

Anthony J. Gill & James G. Kench

University of Oxford, Oxford, UK

Pelvender Gill, Freddie C. Hamdy, Katalin Karaszi, Adam Lambert, Luke Marsden, Clare Verrill & Paresh Vyas

Department of Surgery, Academic Urology Group, University of Cambridge, Cambridge, UK

Vincent J. Gnanapragasam

Department of Medicine II, University of Würzburg, Wuerzburg, Germany

Maria Elisabeth Goebler

Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

Carmen Gomez

Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain

Abel Gonzalez-Perez

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), Durham, NC, USA

Dmitry A. Gordenin & Natalie Saini

St. Thomas’s Hospital, London, UK

James Gossage

Osaka International Cancer Center, Osaka, Japan

Kunihito Gotoh

Department of Pathology, Skåne University Hospital, Lund University, Lund, Sweden

Dorthe Grabau

Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK

Janet S. Graham

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

Eric Green, Carolyn M. Hutter & Heidi J. Sofia

Centre for Cancer Research, Victorian Comprehensive Cancer Centre, University of Melbourne, Melbourne, VIC, Australia

Sean M. Grimmond

Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA

Robert L. Grossman

German Center for Infection Research (DZIF), Partner Site Hamburg-Borstel-Lübeck-Riems, Hamburg, Germany

Adam Grundhoff

Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark

Qianyun Guo, Asger Hobolth & Jakob Skou Pedersen

Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, Delhi, India

Shailja Gupta & K. VijayRaghavan

National Cancer Centre Singapore, Singapore, Singapore

Jonathan Göke

Brandeis University, Waltham, MA, USA

James E. Haber

Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

Department of Internal Medicine, Stanford University, Stanford, CA, USA

Mark P. Hamilton

The University of Texas Health Science Center at Houston, Houston, TX, USA

Leng Han, Yang Yang & Xuanping Zhang

Imperial College NHS Trust, Imperial College, London, INY, UK

George B. Hanna

Senckenberg Institute of Pathology, University of Frankfurt Medical School, Frankfurt, Germany

Martin Hansmann

Department of Medicine, Division of Biomedical Informatics, UC San Diego School of Medicine, San Diego, CA, USA

Olivier Harismendy

Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center, Houston, TX, USA

Arif O. Harmanci

Oxford Nanopore Technologies, New York, NY, USA

Eoghan Harrington & Sissel Juul

Institute of Medical Science, University of Tokyo, Tokyo, Japan

Takanori Hasegawa, Shuto Hayashi, Seiya Imoto, Mitsuhiro Komura, Satoru Miyano, Naoki Miyoshi, Kazuhiro Ohi, Eigo Shimizu, Yuichi Shiraishi, Hiroko Tanaka & Rui Yamaguchi

Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA, USA

David Haussler

Wakayama Medical University, Wakayama, Japan

Shinya Hayami, Masaki Ueno & Hiroki Yamaue

Department of Internal Medicine, Division of Medical Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

D. Neil Hayes

University of Tennessee Health Science Center for Cancer Research, Memphis, TN, USA

Department of Histopathology, Salford Royal NHS Foundation Trust, Salford, UK

Stephen J. Hayes

Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

BIOPIC, ICG and College of Life Sciences, Peking University, Beijing, China

Yao He & Zemin Zhang

Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China

Children’s Hospital of Philadelphia, Philadelphia, PA, USA

Allison P. Heath

Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Apurva M. Hegde, Yiling Lu & John N. Weinstein

Karolinska Institute, Stockholm, Sweden

Eva Hellstrom-Lindberg & Jesper Lagergren

The Donnelly Centre, University of Toronto, Toronto, ON, Canada

Mohamed Helmy & Jeffrey A. Wintersinger

Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon, South Korea

Seong Gu Heo, Eun Pyo Hong & Ji Wan Park

Department of Experimental and Health Sciences, Institute of Evolutionary Biology (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Spain

José María Heredia-Genestar, Tomas Marques-Bonet & Arcadi Navarro

Health Data Science Unit, University Clinics, Heidelberg, Germany

Carl Herrmann

Massachusetts General Hospital Center for Cancer Research, Charlestown, MA, USA

Julian M. Hess & Yosef E. Maruvka

Hokkaido University, Sapporo, Japan

Satoshi Hirano & Toru Nakamura

Department of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan

Nobuyoshi Hiraoka

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Katherine A. Hoadley & Tara J. Skelly

Computational Biology, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany

Steve Hoffmann

University of Melbourne Centre for Cancer Research, Melbourne, VIC, Australia

Oliver Hofmann

University of Nebraska Medical Center, Omaha, NE, USA

Michael A. Hollingsworth & Sarah P. Thayer

Syntekabio Inc, Daejeon, South Korea

Jongwhi H. Hong

Department of Pathology, Academic Medical Center, Amsterdam, AZ, The Netherlands

Gerrit K. Hooijer

China National GeneBank-Shenzhen, Shenzhen, China

Yong Hou, Chang Li, Siliang Li, Xiaobo Li, Dongbing Liu, Xingmin Liu, Henk G. Stunnenberg, Hong Su, Kui Wu, Heng Xiong, Chen Ye & Shida Zhu

Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Volker Hovestadt, Murat Iskar, Peter Lichter, Bernhard Radlwimmer & Marc Zapatka

Division of Life Science and Applied Genomics Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China

Taobo Hu, Yogesh Kumar, Eric Z. Ma, Zhenggang Wu & Hong Xue

Icahn School of Medicine at Mount Sinai, New York, NY, USA

Kuan-lin Huang

Geneplus-Shenzhen, Shenzhen, China

School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, China

Yi Huang, Jiayin Wang, Xiao Xiao & Xuanping Zhang

AbbVie, North Chicago, IL, USA

Thomas J. Hudson

Institute of Pathology, Charité – University Medicine Berlin, Berlin, Germany

Michael Hummel & Dido Lenze

Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, BC, Canada

David Huntsman

Edinburgh Royal Infirmary, Edinburgh, UK

Ted R. Hupp

Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Matthew R. Huska, Julia Markowski & Roland F. Schwarz

Department of Pediatric Immunology, Hematology and Oncology, University Hospital, Heidelberg, Germany

Daniel Hübschmann

Daniel Hübschmann, Christof von Kalle & Roland F. Schwarz

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Heidelberg, Germany

Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA

Marcin Imielinski

Marcin Imielinski & Xiaotong Yao

Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

William B. Isaacs

Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Shumpei Ishikawa, Hiroto Katoh & Daisuke Komura

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Michael Ittmann

Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

Technical University of Denmark, Lyngby, Denmark

Jose M. G. Izarzugaza

Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea

Jocelyne Jacquemier, Hyung-Yong Kim & Gu Kong

Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK

Nigel B. Jamieson

Department of Pathology, Asan Medical Center, College of Medicine, Ulsan University, Songpa-gu, Seoul, South Korea

Se Jin Jang & Hee Jin Lee

Science Writer, Garrett Park, MD, USA

Karine Jegalian

International Cancer Genome Consortium (ICGC)/ICGC Accelerating Research in Genomic Oncology (ARGO) Secretariat, Ontario Institute for Cancer Research, Toronto, ON, Canada

Jennifer L. Jennings

Lara Jerman

Department of Public Health Sciences, University of Chicago, Chicago, IL, USA

Research Institute, NorthShore University HealthSystem, Evanston, IL, USA

Department for Biomedical Research, University of Bern, Bern, Switzerland

Rory Johnson, Andrés Lanzós & Mark A. Rubin

Centre of Genomics and Policy, McGill University and Génome Québec Innovation Centre, Montreal, QC, Canada

Yann Joly, Bartha M. Knoppers, Mark Phillips & Adrian Thorogood

Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Corbin D. Jones

Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany

David T. W. Jones, Marcel Kool & Stefan M. Pfister

Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

David T. W. Jones

Cancer Research UK, London, UK

Nic Jones & David Scott

Indivumed GmbH, Hamburg, Germany

Hartmut Juhl

Genome Integration Data Center, Syntekabio, Inc, Daejeon, South Korea

Jongsun Jung

University Hospital Zurich, Zurich, Switzerland

Andre Kahles, Kjong-Van Lehmann & Gunnar Rätsch

Clinical Bioinformatics, Swiss Institute of Bioinformatics, Geneva, Switzerland

Abdullah Kahraman

Institute for Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland

Abdullah Kahraman & Christian von Mering

MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Edinburgh, UK

Vera B. Kaiser & Colin A. Semple

Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Beth Karlan

Department of Biology, Bioinformatics Group, Division of Molecular Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia

Rosa Karlić

Department for Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Germany

Dennis Karsch & Michael Kneba

Genetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia

Karin S. Kassahn

Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan

Hitoshi Katai

Department of Bioinformatics, Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan

Mamoru Kato, Hirofumi Rokutan & Mihoko Saito-Adachi

A.A. Kharkevich Institute of Information Transmission Problems, Moscow, Russia

Marat D. Kazanov

Oncology and Immunology, Dmitry Rogachev National Research Center of Pediatric Hematology, Moscow, Russia

Skolkovo Institute of Science and Technology, Moscow, Russia

Department of Surgery, The George Washington University, School of Medicine and Health Science, Washington, DC, USA

Electron Kebebew

Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Melanoma Institute Australia, Macquarie University, Sydney, NSW, Australia

Richard F. Kefford

MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA

Manolis Kellis

Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

James G. Kench & Richard A. Scolyer

Cholangiocarcinoma Screening and Care Program and Liver Fluke and Cholangiocarcinoma Research Centre, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

Narong Khuntikeo

Controlled Department and Institution, New York, NY, USA

Ekta Khurana

Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA

Ekta Khurana & Alexander Martinez-Fundichely

National Cancer Center, Gyeonggi, South Korea

Hark Kyun Kim

Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, South Korea

Hyung-Lae Kim

Health Sciences Department of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA

Research Core Center, National Cancer Centre Korea, Goyang-si, South Korea

Jong K. Kim

Department of Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, South Korea

Youngwook Kim

Samsung Genome Institute, Seoul, South Korea

Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA

Tari A. King

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Tari A. King & Samuel Singer

Division of Breast Surgery, Brigham and Women’s Hospital, Boston, MA, USA

Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences (NIEHS), Durham, NC, USA

Leszek J. Klimczak

Department of Clinical Science, University of Bergen, Bergen, Norway

Stian Knappskog & Ola Myklebost

Center For Medical Innovation, Seoul National University Hospital, Seoul, South Korea

Youngil Koh

Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

Youngil Koh & Sung-Soo Yoon

Institute of Computer Science, Polish Academy of Sciences, Warsawa, Poland

Jan Komorowski

Functional and Structural Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Marcel Kool, Andrey Korshunov, Michael Koscher, Stefan M. Pfister & Qi Wang

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, , National Institutes of Health, Bethesda, MD, USA

Roelof Koster

Institute for Medical Informatics Statistics and Epidemiology, University of Leipzig, Leipzig, Germany

Markus Kreuz & Markus Loeffler

Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Savitri Krishnamurthy

Department of Hematology and Oncology, Georg-Augusts-University of Göttingen, Göttingen, Germany

Dieter Kube & Lorenz H. P. Trümper

Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany

Ralf Küppers

King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

Jesper Lagergren

Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA

Peter W. Laird

The University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

Sunil R. Lakhani & Peter T. Simpson

Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany

Pablo Landgraf

University of Düsseldorf, Düsseldorf, Germany

Pablo Landgraf & Guido Reifenberger

Department of Pathology, Institut Jules Bordet, Brussels, Belgium

Denis Larsimont

Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

Erik Larsson

Children’s Medical Research Institute, Sydney, NSW, Australia

Loretta M. S. Lau & Hilda A. Pickett

ILSbio, LLC Biobank, Chestertown, MD, USA

Division of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

Eunjung Alice Lee

Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, South Korea

Jeong-Yeon Lee

Department of Statistics, University of California Santa Cruz, Santa Cruz, CA, USA

National Genotyping Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Ming Ta Michael Lee

Department of Vertebrate Genomics/Otto Warburg Laboratory Gene Regulation and Systems Biology of Cancer, Max Planck Institute for Molecular Genetics, Berlin, Germany

Hans Lehrach, Hans-Jörg Warnatz & Marie-Laure Yaspo

McGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada

Louis Letourneau

biobyte solutions GmbH, Heidelberg, Germany

Ivica Letunic

Gynecologic Oncology, NYU Laura and Isaac Perlmutter Cancer Center, New York University, New York, NY, USA

Douglas A. Levine

Division of Oncology, Stem Cell Biology Section, Washington University School of Medicine, St. Louis, MO, USA

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Harvard University, Cambridge, MA, USA

Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

W. M. Linehan

University of Oslo, Oslo, Norway

Ole Christian Lingjærde & Torill Sauer

University of Toronto, Toronto, ON, Canada

Fei-Fei Fei Liu, Quaid D. Morris, Ruian Shi, Shankar Vembu & Fan Yang

Peking University, Beijing, China

Fenglin Liu, Fan Zhang, Liangtao Zheng & Xiuqing Zheng

School of Life Sciences, Peking University, Beijing, China

Fenglin Liu

Leidos Biomedical Research, Inc, McLean, VA, USA

Hematology, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

Armando Lopez-Guillermo

Second Military Medical University, Shanghai, China

Yong-Jie Lu & Hongwei Zhang

Chinese Cancer Genome Consortium, Shenzhen, China

Department of Medical Oncology, Beijing Hospital, Beijing, China

Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China

Youyong Lu & Rui Xing

School of Medicine/School of Mathematics and Statistics, University of St. Andrews, St, Andrews, Fife, UK

Andy G. Lynch

Institute for Systems Biology, Seattle, WA, USA

Lisa Lype, Sheila M. Reynolds & Ilya Shmulevich

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University Institute of Oncology-IUOPA, Oviedo, Spain

Carlos López-Otín & Xose S. Puente

Institut Bergonié, Bordeaux, France

Gaetan MacGrogan

Cancer Unit, MRC University of Cambridge, Cambridge, UK

Shona MacRae

Department of Pathology and Laboratory Medicine, Center for Personalized Medicine, Children’s Hospital Los Angeles, Los Angeles, CA, USA

Dennis T. Maglinte

John Curtin School of Medical Research, Canberra, ACT, Australia

Graham J. Mann

MVZ Department of Oncology, PraxisClinic am Johannisplatz, Leipzig, Germany

Luisa Mantovani-Löffler

Department of Information Technology, Ghent University, Ghent, Belgium

Kathleen Marchal & Sergio Pulido-Tamayo

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium

Kathleen Marchal, Sergio Pulido-Tamayo & Lieven P. C. Verbeke

Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

Elaine R. Mardis

Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR, USA

Adam A. Margolin & Adam J. Struck

Department of Surgery, Duke University, Durham, NC, USA

Jeffrey Marks

Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

Tomas Marques-Bonet, Jose I. Martin-Subero, Arcadi Navarro, David Torrents & Alfonso Valencia

Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Barcelona, Spain

Tomas Marques-Bonet

Sancha Martin & Ke Yuan

Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

Jose I. Martin-Subero

Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA

R. Jay Mashl

Department of Surgery and Cancer, Imperial College, London, INY, UK

Applications Department, Oxford Nanopore Technologies, Oxford, UK

Simon Mayes & Daniel J. Turner

Department of Obstetrics, Gynecology and Reproductive Services, University of California San Francisco, San Francisco, CA, USA

Karen McCune & Karen Smith-McCune

Department of Biochemistry and Molecular Medicine, University California at Davis, Sacramento, CA, USA

John D. McPherson

STTARR Innovation Facility, Princess Margaret Cancer Centre, Toronto, ON, Canada

Discipline of Surgery, Western Sydney University, Penrith, NSW, Australia

Neil D. Merrett

Yale School of Medicine, Yale University, New Haven, CT, USA

William Meyerson

Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Piotr A. Mieczkowski, Joel S. Parker, Charles M. Perou, Donghui Tan, Umadevi Veluvolu & Matthew D. Wilkerson

Departments of Neurology and Neurosurgery, Henry Ford Hospital, Detroit, MI, USA

Tom Mikkelsen

Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

Gordon B. Mills

Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Sarah Minner, Guido Sauter & Ronald Simon

Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

Shinichi Mizuno

Heidelberg Academy of Sciences and Humanities, Heidelberg, Germany

Fruzsina Molnár-Gábor

Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia

Carl Morrison, Karin A. Oien, Chawalit Pairojkul, Paul M. Waring & Marc J. van de Vijver

Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA

Carl Morrison

Department of Computer Science, University of Helsinki, Helsinki, Finland

Ville Mustonen

Institute of Biotechnology, University of Helsinki, Helsinki, Finland

Organismal and Evolutionary Biology Research Programme, University of Helsinki, Helsinki, Finland

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, MO, USA

David Mutch

Penrose St. Francis Health Services, Colorado Springs, CO, USA

Jerome Myers

Institute of Pathology, Ulm University and University Hospital of Ulm, Ulm, Germany

Peter Möller

National Cancer Center, Tokyo, Japan

Hitoshi Nakagama

Genome Institute of Singapore, Singapore, Singapore

Tannistha Nandi & Patrick Tan

32Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA

Fabio C. P. Navarro

German Cancer Aid, Bonn, Germany

Gerd Nettekoven & Laura Planko

Programme in Cancer and Stem Cell Biology, Centre for Computational Biology, Duke-NUS Medical School, Singapore, Singapore

Alvin Wei Tian Ng

The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China

Fourth Military Medical University, Shaanxi, China

Yongzhan Nie

The University of Cambridge School of Clinical Medicine, Cambridge, UK

Serena Nik-Zainal

St. Jude Children’s Research Hospital, Memphis, TN, USA

Paul A. Northcott

University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada

Faiyaz Notta & Ming Tsao

Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA, USA

Brian D. O’Connor

Department of Medicine, University of Chicago, Chicago, IL, USA

Peter O’Donnell

Department of Neurology, Mayo Clinic, Rochester, MN, USA

Brian Patrick O’Neill

Cambridge Oesophagogastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

J. Robert O’Neill

Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

Karin A. Oien

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

Akinyemi I. Ojesina

HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA

O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

Department of Pathology, Keio University School of Medicine, Tokyo, Japan

Hidenori Ojima

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan

Takuji Okusaka

Sage Bionetworks, Seattle, WA, USA

Larsson Omberg

Lymphoma Genomic Translational Research Laboratory, National Cancer Centre, Singapore, Singapore

Choon Kiat Ong

Department of Clinical Pathology, Robert-Bosch-Hospital, Stuttgart, Germany

Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada

B. F. Francis Ouellette

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

Qiang Pan-Hammarström

Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Gyeonggi, South Korea

Joong-Won Park

Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Keunchil Park

Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, South Korea

Cheonan Industry-Academic Collaboration Foundation, Sangmyung University, Cheonan, South Korea

Kiejung Park

NYU Langone Medical Center, New York, NY, USA

Harvey Pass

Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA

Nathan A. Pennell

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA

Marc D. Perry

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

Gloria M. Petersen

Helen F. Graham Cancer Center at Christiana Care Health Systems, Newark, DE, USA

Nicholas Petrelli

Heidelberg University Hospital, Heidelberg, Germany

Stefan M. Pfister

CSRA Incorporated, Fairfax, VA, USA

Todd D. Pihl

Research Department of Pathology, University College London Cancer Institute, London, UK

Nischalan Pillay

Department of Research Oncology, Guy’s Hospital, King’s Health Partners AHSC, King’s College London School of Medicine, London, UK

Sarah Pinder

Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia

Andreia V. Pinho

University Hospital of Minjoz, INSERM UMR 1098, Besançon, France

Xavier Pivot

Spanish National Cancer Research Centre, Madrid, Spain

Center of Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania

Irinel Popescu

Cureline, Inc, South San Francisco, CA, USA

Olga Potapova

St. Luke’s Cancer Centre, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK

Shaun R. Preston

Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge, UK

Elena Provenzano

East of Scotland Breast Service, Ninewells Hospital, Aberdeen, UK

Colin A. Purdie

Department of Genetics, Microbiology and Statistics, University of Barcelona, IRSJD, IBUB, Barcelona, Spain

Raquel Rabionet

Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, USA

Janet S. Rader

Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA

Suresh Ramalingam

Benjamin J. Raphael & Matthew A. Reyna

Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA

W. Kimryn Rathmell

Ohio State University College of Medicine and Arthur G. James Comprehensive Cancer Center, Columbus, OH, USA

Matthew Ringel

Department of Surgery, Yokohama City University Graduate School of Medicine, Kanagawa, Japan

Yasushi Rino

Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany

Karsten Rippe

Research Computing Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Jeffrey Roach

School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA, USA

Steven A. Roberts

Finsen Laboratory and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark

F. Germán Rodríguez-González, Nikos Sidiropoulos & Joachim Weischenfeldt

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

Michael H. A. Roehrl & Stefano Serra

Department of Pathology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Michael H. A. Roehrl

University Hospital Giessen, Pediatric Hematology and Oncology, Giessen, Germany

Marius Rohde

Oncologie Sénologie, ICM Institut Régional du Cancer, Montpellier, France

Gilles Romieu

Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

Philip C. Rosenstiel & Markus B. Schilhabel

Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany

Andreas Rosenwald

Department of Urology, North Bristol NHS Trust, Bristol, UK

Edward W. Rowe

SingHealth, Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore, Singapore

Steven G. Rozen, Patrick Tan & Bin Tean Teh

Department of Computer Science, University of Toronto, Toronto, ON, Canada

Yulia Rubanova, Jared T. Simpson & Jeffrey A. Wintersinger

Bern Center for Precision Medicine, University Hospital of Bern, University of Bern, Bern, Switzerland

Mark A. Rubin

Englander Institute for Precision Medicine, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY, USA

Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

Pathology and Laboratory, Weill Cornell Medical College, New York, NY, USA

Vall d’Hebron Institute of Oncology: VHIO, Barcelona, Spain

Carlota Rubio-Perez

General and Hepatobiliary-Biliary Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy

Andrea Ruzzenente

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India

Radhakrishnan Sabarinathan

S. Cenk Sahinalp

Department of Pathology, GZA-ZNA Hospitals, Antwerp, Belgium

Roberto Salgado

Analytical Biological Services, Inc, Wilmington, DE, USA

Charles Saller

Sydney Medical School, University of Sydney, Sydney, NSW, Australia

Jaswinder S. Samra & Richard A. Scolyer

cBio Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Chris Sander & Ciyue Shen

Department of Cell Biology, Harvard Medical School, Boston, MA, USA

Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India

Rajiv Sarin

School of Environmental and Life Sciences, Faculty of Science, The University of Newcastle, Ourimbah, NSW, Australia

Christopher J. Scarlett

Department of Dermatology, University Hospital of Essen, Essen, Germany

Dirk Schadendorf

Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Matthias Schlesner

Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany

Thorsten Schlomm & Joachim Weischenfeldt

Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Thorsten Schlomm

Department of General Internal Medicine, University of Kiel, Kiel, Germany

Stefan Schreiber

German Cancer Consortium (DKTK), Partner site Berlin, Berlin, Germany

Roland F. Schwarz

Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA

Ralph Scully

University of Pittsburgh, Pittsburgh, PA, USA

Raja Seethala

Department of Ophthalmology and Ocular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA

Ayellet V. Segre

Center for Psychiatric Genetics, NorthShore University HealthSystem, Evanston, IL, USA

Subhajit Sengupta

Van Andel Research Institute, Grand Rapids, MI, USA

Hui Shen & Wanding Zhou

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Tatsuhiro Shibata, Hirokazu Taniguchi & Tomoko Urushidate

Japan Agency for Medical Research and Development, Tokyo, Japan

Kiyo Shimizu & Takashi Yugawa

Seung Jun Shin & Stefan G. Stark

Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA

Craig Shriver

Human Genetics, University of Kiel, Kiel, Germany

Reiner Siebert

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Sabina Signoretti

Oregon Health and Science University, Portland, OR, USA

Jaclyn Smith

Center for RNA Interference and Noncoding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Anil K. Sood

Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

Sharmila Sothi

Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, GA, The Netherlands

Paul N. Span

Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA

Jonathan Spring

Clinic for Hematology and Oncology, St.-Antonius-Hospital, Eschweiler, Germany

Peter Staib

Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Stefan G. Stark

University of Iceland, Reykjavik, Iceland

Ólafur Andri Stefánsson

Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Oliver Stegle

Dundee Cancer Centre, Ninewells Hospital, Dundee, UK

Alasdair Stenhouse & Alastair M. Thompson

Department for Internal Medicine III, University of Ulm and University Hospital of Ulm, Ulm, Germany

Stephan Stilgenbauer

Institut Curie, INSERM Unit 830, Paris, France

Henk G. Stunnenberg & Anne Vincent-Salomon

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan

Akihiro Suzuki

Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, GA, The Netherlands

Division of Cancer Genome Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

Holger Sültmann

Department of General Surgery, Singapore General Hospital, Singapore, Singapore

Benita Kiat Tee Tan

Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

Patrick Tan & Bin Tean Teh

Department of Medical and Clinical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland

Tomas J. Tanskanen

East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Patrick Tarpey

Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA

Simon Tavaré

Institute of Molecular and Cell Biology, Singapore, Singapore

Bin Tean Teh

Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Centre Singapore, Singapore, Singapore

Universite Lyon, INCa-Synergie, Centre Léon Bérard, Lyon, France

Gilles Thomas

Department of Urology, Mayo Clinic, Rochester, MN, USA

R. Houston Thompson

Royal National Orthopaedic Hospital - Stanmore, Stanmore, Middlesex, UK

Roberto Tirabosco

Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain

Giovanni Paolo II / I.R.C.C.S. Cancer Institute, Bari, BA, Italy

Stefania Tommasi

Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany

Umut H. Toprak

Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy, Rome, Italy

Giampaolo Tortora

University of Verona, Verona, Italy

Centre National de Génotypage, CEA - Institute de Génomique, Evry, France

CAPHRI Research School, Maastricht University, Maastricht, ER, The Netherlands

David Townend

Department of Biopathology, Centre Léon Bérard, Lyon, France

Isabelle Treilleux

Université Claude Bernard Lyon 1, Villeurbanne, France

Core Research for Evolutional Science and Technology (CREST), JST, Tokyo, Japan

Tatsuhiko Tsunoda

Department of Biological Sciences, Laboratory for Medical Science Mathematics, Graduate School of Science, University of Tokyo, Yokohama, Japan

Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Hinxton, UK

Jose M. C. Tubio

University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

Olga Tucker

Centre for Cancer Research and Cell Biology, Queen’s University, Belfast, UK

Richard Turkington

Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Naoto T. Ueno

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Christopher Umbricht

Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden

Husen M. Umer

School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK

Timothy J. Underwood

Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia

Liis Uusküla-Reimand

Genetics and Genome Biology Program, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON, Canada

Departments of Neurosurgery and Hematology and Medical Oncology, Winship Cancer Institute and School of Medicine, Emory University, Atlanta, GA, USA

Erwin G. Van Meir

Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway

Miguel Vazquez

Argmix Consulting, North Vancouver, BC, Canada

Shankar Vembu

Department of Information Technology, Ghent University, Interuniversitair Micro-Electronica Centrum (IMEC), Ghent, Belgium

Lieven P. C. Verbeke

Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK

Clare Verrill

Institute of Mathematics and Computer Science, University of Latvia, Riga, LV, Latvia

Juris Viksna

Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia

Ricardo E. Vilain

Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, UK

Ignacio Vázquez-García

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ignacio Vázquez-García & Venkata D. Yellapantula

Department of Statistics, Columbia University, New York, NY, USA

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

Claes Wadelius

School of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, China

Jiayin Wang & Kai Ye

Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Anne Y. Warren

Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK

David C. Wedge

Georgia Regents University Cancer Center, Augusta, GA, USA

Paul Weinberger

Wythenshawe Hospital, Manchester, UK

Department of Genetics, Washington University School of Medicine, St.Louis, MO, USA

Michael C. Wendl

Department of Biological Oceanography, Leibniz Institute of Baltic Sea Research, Rostock, Germany

Johannes Werner

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK

Justin P. Whalley

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

Thoracic Oncology Laboratory, Mayo Clinic, Rochester, MN, USA

Dennis Wigle

Richard K. Wilson

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA

Boris Winterhoff

International Institute for Molecular Oncology, Poznań, Poland

Maciej Wiznerowicz

Poznan University of Medical Sciences, Poznań, Poland

Genomics and Proteomics Core Facility High Throughput Sequencing Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany

Stephan Wolf

NCCS-VARI Translational Research Laboratory, National Cancer Centre Singapore, Singapore, Singapore

Bernice H. Wong

Edison Family Center for Genome Sciences and Systems Biology, Washington University, St. Louis, MO, USA

Winghing Wong

MRC-University of Glasgow Centre for Virus Research, Glasgow, UK

Derek W. Wright

Department of Medical Informatics and Clinical Epidemiology, Division of Bioinformatics and Computational Biology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

Guanming Wu

School of Electronic Information and Communications, Huazhong University of Science and Technology, Wuhan, China

Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA

Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan

Shinichi Yachida

Institute of Computer Science, Heidelberg University, Heidelberg, Germany

Sergei Yakneen

School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia

Jean Y. Yang

Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA

Lixing Yang

Department of Human Genetics, University of Chicago, Chicago, IL, USA

Tri-Institutional PhD Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY, USA

Xiaotong Yao

The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Kaixian Yu & Hongtu Zhu

Duke-NUS Medical School, Singapore, Singapore

Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

School of Computing Science, University of Glasgow, Glasgow, UK

Division of Orthopaedic Surgery, Oslo University Hospital, Oslo, Norway

Olga Zaikova

Eastern Clinical School, Monash University, Melbourne, VIC, Australia

Nikolajs Zeps

Epworth HealthCare, Richmond, VIC, Australia

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

Cheng-Zhong Zhang

Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA

The Ohio State University Comprehensive Cancer Center (OSUCCC – James), Columbus, OH, USA

The University of Texas School of Biomedical Informatics (SBMI) at Houston, Houston, TX, USA

Zhongming Zhao

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Anna deFazio

Department of Pathology, Erasmus Medical Center Rotterdam, Rotterdam, GD, The Netherlands

Carolien H. M. van Deurzen

Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, CX, The Netherlands

L. van’t Veer

Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland

Christian von Mering

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  • , Niedzica Camacho
  • , Elias Campo
  • , Cinzia Cantù
  • , Thomas E. Carey
  • , Joana Carlevaro-Fita
  • , Rebecca Carlsen
  • , Ivana Cataldo
  • , Mario Cazzola
  • , Jonathan Cebon
  • , Robert Cerfolio
  • , Dianne E. Chadwick
  • , Dimple Chakravarty
  • , Don Chalmers
  • , Calvin Wing Yiu Chan
  • , Michelle Chan-Seng-Yue
  • , Vishal S. Chandan
  • , David K. Chang
  • , Stephen J. Chanock
  • , Lorraine A. Chantrill
  • , Aurélien Chateigner
  • , Nilanjan Chatterjee
  • , Kazuaki Chayama
  • , Hsiao-Wei Chen
  • , Jieming Chen
  • , Yiwen Chen
  • , Zhaohong Chen
  • , Andrew D. Cherniack
  • , Jeremy Chien
  • , Yoke-Eng Chiew
  • , Suet-Feung Chin
  • , Sunghoon Cho
  • , Jung Kyoon Choi
  • , Christine Chomienne
  • , Zechen Chong
  • , Su Pin Choo
  • , Angela Chou
  • , Angelika N. Christ
  • , Eric Chuah
  • , Carrie Cibulskis
  • , Kristian Cibulskis
  • , Sara Cingarlini
  • , Peter Clapham
  • , Alexander Claviez
  • , Sean Cleary
  • , Nicole Cloonan
  • , Colin C. Collins
  • , Ashton A. Connor
  • , Susanna L. Cooke
  • , Colin S. Cooper
  • , Leslie Cope
  • , Vincenzo Corbo
  • , Matthew G. Cordes
  • , Stephen M. Cordner
  • , Isidro Cortés-Ciriano
  • , Kyle Covington
  • , Prue A. Cowin
  • , Brian Craft
  • , David Craft
  • , Chad J. Creighton
  • , Erin Curley
  • , Ioana Cutcutache
  • , Karolina Czajka
  • , Bogdan Czerniak
  • , Rebecca A. Dagg
  • , Ludmila Danilova
  • , Maria Vittoria Davi
  • , Natalie R. Davidson
  • , Helen Davies
  • , Ian J. Davis
  • , Brandi N. Davis-Dusenbery
  • , Francisco M. De La Vega
  • , Ricardo De Paoli-Iseppi
  • , Timothy Defreitas
  • , Angelo P. Dei Tos
  • , Olivier Delaneau
  • , John A. Demchok
  • , German M. Demidov
  • , Deniz Demircioğlu
  • , Nening M. Dennis
  • , Robert E. Denroche
  • , Stefan C. Dentro
  • , Nikita Desai
  • , Vikram Deshpande
  • , Christine Desmedt
  • , Jordi Deu-Pons
  • , Noreen Dhalla
  • , Neesha C. Dhani
  • , Priyanka Dhingra
  • , Rajiv Dhir
  • , Anthony DiBiase
  • , Klev Diamanti
  • , Shuai Ding
  • , Huy Q. Dinh
  • , Luc Dirix
  • , HarshaVardhan Doddapaneni
  • , Michelle T. Dow
  • , Ronny Drapkin
  • , Oliver Drechsel
  • , Serge Serge
  • , Tim Dudderidge
  • , Ana Dueso-Barroso
  • , Andrew J. Dunford
  • , Michael Dunn
  • , Lewis Jonathan Dursi
  • , Fraser R. Duthie
  • , Ken Dutton-Regester
  • , Jenna Eagles
  • , Douglas F. Easton
  • , Stuart Edmonds
  • , Paul A. Edwards
  • , Sandra E. Edwards
  • , Rosalind A. Eeles
  • , Anna Ehinger
  • , Juergen Eils
  • , Adel El-Naggar
  • , Matthew Eldridge
  • , Kyle Ellrott
  • , Serap Erkek
  • , Georgia Escaramis
  • , Shadrielle M. G. Espiritu
  • , Xavier Estivill
  • , Dariush Etemadmoghadam
  • , Jorunn E. Eyfjord
  • , Bishoy M. Faltas
  • , Daiming Fan
  • , William C. Faquin
  • , Claudiu Farcas
  • , Matteo Fassan
  • , Aquila Fatima
  • , Francesco Favero
  • , Nodirjon Fayzullaev
  • , Ina Felau
  • , Sian Fereday
  • , Martin L. Ferguson
  • , Vincent Ferretti
  • , Lars Feuerbach
  • , Matthew A. Field
  • , J. Lynn Fink
  • , Gaetano Finocchiaro
  • , Cyril Fisher
  • , Matthew W. Fittall
  • , Anna Fitzgerald
  • , Rebecca C. Fitzgerald
  • , Adrienne M. Flanagan
  • , Neil E. Fleshner
  • , Paul Flicek
  • , John A. Foekens
  • , Kwun M. Fong
  • , Nuno A. Fonseca
  • , Christopher S. Foster
  • , Natalie S. Fox
  • , Michael Fraser
  • , Scott Frazer
  • , Milana Frenkel-Morgenstern
  • , William Friedman
  • , Joan Frigola
  • , Catrina C. Fronick
  • , Akihiro Fujimoto
  • , Masashi Fujita
  • , Masashi Fukayama
  • , Lucinda A. Fulton
  • , Robert S. Fulton
  • , Mayuko Furuta
  • , P. Andrew Futreal
  • , Anja Füllgrabe
  • , Stacey B. Gabriel
  • , Steven Gallinger
  • , Carlo Gambacorti-Passerini
  • , Jianjiong Gao
  • , Shengjie Gao
  • , Levi Garraway
  • , Øystein Garred
  • , Erik Garrison
  • , Nils Gehlenborg
  • , Josep L. L. Gelpi
  • , Joshy George
  • , Daniela S. Gerhard
  • , Clarissa Gerhauser
  • , Jeffrey E. Gershenwald
  • , Mark Gerstein
  • , Mohammed Ghori
  • , Ronald Ghossein
  • , Nasra H. Giama
  • , Richard A. Gibbs
  • , Bob Gibson
  • , Anthony J. Gill
  • , Pelvender Gill
  • , Dilip D. Giri
  • , Dominik Glodzik
  • , Vincent J. Gnanapragasam
  • , Maria Elisabeth Goebler
  • , Mary J. Goldman
  • , Carmen Gomez
  • , Abel Gonzalez-Perez
  • , Dmitry A. Gordenin
  • , James Gossage
  • , Kunihito Gotoh
  • , Ramaswamy Govindan
  • , Dorthe Grabau
  • , Janet S. Graham
  • , Robert C. Grant
  • , Anthony R. Green
  • , Eric Green
  • , Liliana Greger
  • , Nicola Grehan
  • , Sonia Grimaldi
  • , Sean M. Grimmond
  • , Robert L. Grossman
  • , Adam Grundhoff
  • , Gunes Gundem
  • , Qianyun Guo
  • , Manaswi Gupta
  • , Shailja Gupta
  • , Ivo G. Gut
  • , Marta Gut
  • , Jonathan Göke
  • , Andrea Haake
  • , David Haan
  • , Siegfried Haas
  • , James E. Haber
  • , Nina Habermann
  • , Faraz Hach
  • , Syed Haider
  • , Natsuko Hama
  • , Freddie C. Hamdy
  • , Anne Hamilton
  • , Mark P. Hamilton
  • , George B. Hanna
  • , Martin Hansmann
  • , Nicholas J. Haradhvala
  • , Olivier Harismendy
  • , Ivon Harliwong
  • , Arif O. Harmanci
  • , Eoghan Harrington
  • , Takanori Hasegawa
  • , David Haussler
  • , Steve Hawkins
  • , Shinya Hayami
  • , Shuto Hayashi
  • , D. Neil Hayes
  • , Stephen J. Hayes
  • , Nicholas K. Hayward
  • , Steven Hazell
  • , Allison P. Heath
  • , Simon C. Heath
  • , David Hedley
  • , Apurva M. Hegde
  • , David I. Heiman
  • , Michael C. Heinold
  • , Zachary Heins
  • , Lawrence E. Heisler
  • , Eva Hellstrom-Lindberg
  • , Mohamed Helmy
  • , Seong Gu Heo
  • , Austin J. Hepperla
  • , José María Heredia-Genestar
  • , Carl Herrmann
  • , Peter Hersey
  • , Julian M. Hess
  • , Holmfridur Hilmarsdottir
  • , Jonathan Hinton
  • , Satoshi Hirano
  • , Nobuyoshi Hiraoka
  • , Katherine A. Hoadley
  • , Asger Hobolth
  • , Ermin Hodzic
  • , Jessica I. Hoell
  • , Steve Hoffmann
  • , Oliver Hofmann
  • , Andrea Holbrook
  • , Aliaksei Z. Holik
  • , Michael A. Hollingsworth
  • , Oliver Holmes
  • , Robert A. Holt
  • , Chen Hong
  • , Eun Pyo Hong
  • , Jongwhi H. Hong
  • , Gerrit K. Hooijer
  • , Henrik Hornshøj
  • , Fumie Hosoda
  • , Volker Hovestadt
  • , William Howat
  • , Alan P. Hoyle
  • , Ralph H. Hruban
  • , Jianhong Hu
  • , Kuan-lin Huang
  • , Mei Huang
  • , Mi Ni Huang
  • , Vincent Huang
  • , Wolfgang Huber
  • , Thomas J. Hudson
  • , Michael Hummel
  • , Jillian A. Hung
  • , David Huntsman
  • , Ted R. Hupp
  • , Jason Huse
  • , Matthew R. Huska
  • , Barbara Hutter
  • , Carolyn M. Hutter
  • , Daniel Hübschmann
  • , Christine A. Iacobuzio-Donahue
  • , Charles David Imbusch
  • , Seiya Imoto
  • , William B. Isaacs
  • , Keren Isaev
  • , Shumpei Ishikawa
  • , Murat Iskar
  • , S. M. Ashiqul Islam
  • , Michael Ittmann
  • , Sinisa Ivkovic
  • , Jose M. G. Izarzugaza
  • , Jocelyne Jacquemier
  • , Valerie Jakrot
  • , Nigel B. Jamieson
  • , Gun Ho Jang
  • , Se Jin Jang
  • , Joy C. Jayaseelan
  • , Reyka Jayasinghe
  • , Stuart R. Jefferys
  • , Karine Jegalian
  • , Jennifer L. Jennings
  • , Seung-Hyup Jeon
  • , Peter A. Johansson
  • , Amber L. Johns
  • , Jeremy Johns
  • , Rory Johnson
  • , Todd A. Johnson
  • , Yann Joly
  • , Jon G. Jonasson
  • , Corbin D. Jones
  • , David R. Jones
  • , David T. W. Jones
  • , Nic Jones
  • , Steven J. M. Jones
  • , Jos Jonkers
  • , Young Seok Ju
  • , Hartmut Juhl
  • , Jongsun Jung
  • , Malene Juul
  • , Randi Istrup Juul
  • , Sissel Juul
  • , Natalie Jäger
  • , Rolf Kabbe
  • , Andre Kahles
  • , Abdullah Kahraman
  • , Vera B. Kaiser
  • , Hojabr Kakavand
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  • , Christof von Kalle
  • , Koo Jeong Kang
  • , Katalin Karaszi
  • , Beth Karlan
  • , Rosa Karlić
  • , Dennis Karsch
  • , Katayoon Kasaian
  • , Karin S. Kassahn
  • , Hitoshi Katai
  • , Mamoru Kato
  • , Hiroto Katoh
  • , Yoshiiku Kawakami
  • , Jonathan D. Kay
  • , Stephen H. Kazakoff
  • , Marat D. Kazanov
  • , Maria Keays
  • , Electron Kebebew
  • , Richard F. Kefford
  • , Manolis Kellis
  • , James G. Kench
  • , Catherine J. Kennedy
  • , Jules N. A. Kerssemakers
  • , David Khoo
  • , Vincent Khoo
  • , Narong Khuntikeo
  • , Ekta Khurana
  • , Helena Kilpinen
  • , Hark Kyun Kim
  • , Hyung-Lae Kim
  • , Hyung-Yong Kim
  • , Hyunghwan Kim
  • , Jaegil Kim
  • , Jihoon Kim
  • , Jong K. Kim
  • , Youngwook Kim
  • , Tari A. King
  • , Wolfram Klapper
  • , Leszek J. Klimczak
  • , Stian Knappskog
  • , Michael Kneba
  • , Bartha M. Knoppers
  • , Youngil Koh
  • , Jan Komorowski
  • , Daisuke Komura
  • , Mitsuhiro Komura
  • , Marcel Kool
  • , Jan O. Korbel
  • , Viktoriya Korchina
  • , Andrey Korshunov
  • , Michael Koscher
  • , Roelof Koster
  • , Zsofia Kote-Jarai
  • , Antonios Koures
  • , Milena Kovacevic
  • , Barbara Kremeyer
  • , Helene Kretzmer
  • , Markus Kreuz
  • , Savitri Krishnamurthy
  • , Dieter Kube
  • , Kiran Kumar
  • , Pardeep Kumar
  • , Sushant Kumar
  • , Yogesh Kumar
  • , Ritika Kundra
  • , Kirsten Kübler
  • , Ralf Küppers
  • , Jesper Lagergren
  • , Phillip H. Lai
  • , Peter W. Laird
  • , Sunil R. Lakhani
  • , Christopher M. Lalansingh
  • , Emilie Lalonde
  • , Fabien C. Lamaze
  • , Adam Lambert
  • , Eric Lander
  • , Pablo Landgraf
  • , Luca Landoni
  • , Anita Langerød
  • , Andrés Lanzós
  • , Denis Larsimont
  • , Erik Larsson
  • , Mark Lathrop
  • , Loretta M. S. Lau
  • , Chris Lawerenz
  • , Rita T. Lawlor
  • , Michael S. Lawrence
  • , Alexander J. Lazar
  • , Ana Mijalkovic Lazic
  • , Darlene Lee
  • , Donghoon Lee
  • , Eunjung Alice Lee
  • , Hee Jin Lee
  • , Jake June-Koo Lee
  • , Jeong-Yeon Lee
  • , Ming Ta Michael Lee
  • , Kjong-Van Lehmann
  • , Hans Lehrach
  • , Dido Lenze
  • , Conrad R. Leonard
  • , Daniel A. Leongamornlert
  • , Louis Letourneau
  • , Ivica Letunic
  • , Douglas A. Levine
  • , Lora Lewis
  • , Constance H. Li
  • , Haiyan Irene Li
  • , Shantao Li
  • , Siliang Li
  • , Xiaobo Li
  • , Xiaotong Li
  • , Xinyue Li
  • , Yilong Li
  • , Han Liang
  • , Sheng-Ben Liang
  • , Peter Lichter
  • , W. M. Linehan
  • , Ole Christian Lingjærde
  • , Dongbing Liu
  • , Eric Minwei Liu
  • , Fei-Fei Fei Liu
  • , Fenglin Liu
  • , Xingmin Liu
  • , Julie Livingstone
  • , Dimitri Livitz
  • , Naomi Livni
  • , Lucas Lochovsky
  • , Markus Loeffler
  • , Georgina V. Long
  • , Armando Lopez-Guillermo
  • , Shaoke Lou
  • , David N. Louis
  • , Laurence B. Lovat
  • , Yiling Lu
  • , Yong-Jie Lu
  • , Youyong Lu
  • , Claudio Luchini
  • , Ilinca Lungu
  • , Xuemei Luo
  • , Hayley J. Luxton
  • , Andy G. Lynch
  • , Lisa Lype
  • , Cristina López
  • , Carlos López-Otín
  • , Eric Z. Ma
  • , Yussanne Ma
  • , Gaetan MacGrogan
  • , Shona MacRae
  • , Tobias Madsen
  • , Kazuhiro Maejima
  • , Andrea Mafficini
  • , Dennis T. Maglinte
  • , Arindam Maitra
  • , Partha P. Majumder
  • , Luca Malcovati
  • , Giuseppe Malleo
  • , Graham J. Mann
  • , Luisa Mantovani-Löffler
  • , Kathleen Marchal
  • , Giovanni Marchegiani
  • , Elaine R. Mardis
  • , Adam A. Margolin
  • , Maximillian G. Marin
  • , Julia Markowski
  • , Jeffrey Marks
  • , Tomas Marques-Bonet
  • , Marco A. Marra
  • , Luke Marsden
  • , John W. M. Martens
  • , Sancha Martin
  • , Jose I. Martin-Subero
  • , Iñigo Martincorena
  • , Alexander Martinez-Fundichely
  • , Yosef E. Maruvka
  • , R. Jay Mashl
  • , Charlie E. Massie
  • , Thomas J. Matthew
  • , Lucy Matthews
  • , Erik Mayer
  • , Simon Mayes
  • , Michael Mayo
  • , Faridah Mbabaali
  • , Karen McCune
  • , Ultan McDermott
  • , Patrick D. McGillivray
  • , Michael D. McLellan
  • , John D. McPherson
  • , John R. McPherson
  • , Treasa A. McPherson
  • , Samuel R. Meier
  • , Alice Meng
  • , Shaowu Meng
  • , Andrew Menzies
  • , Neil D. Merrett
  • , Sue Merson
  • , Matthew Meyerson
  • , William Meyerson
  • , Piotr A. Mieczkowski
  • , George L. Mihaiescu
  • , Sanja Mijalkovic
  • , Tom Mikkelsen
  • , Michele Milella
  • , Linda Mileshkin
  • , Christopher A. Miller
  • , David K. Miller
  • , Jessica K. Miller
  • , Gordon B. Mills
  • , Ana Milovanovic
  • , Sarah Minner
  • , Marco Miotto
  • , Gisela Mir Arnau
  • , Lisa Mirabello
  • , Chris Mitchell
  • , Satoru Miyano
  • , Naoki Miyoshi
  • , Shinichi Mizuno
  • , Fruzsina Molnár-Gábor
  • , Malcolm J. Moore
  • , Richard A. Moore
  • , Sandro Morganella
  • , Carl Morrison
  • , Lisle E. Mose
  • , Catherine D. Moser
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  • , Loris Mularoni
  • , Andrew J. Mungall
  • , Karen Mungall
  • , Elizabeth A. Musgrove
  • , David Mutch
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  • , Donna M. Muzny
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  • , Jerome Myers
  • , Ola Myklebost
  • , Peter Möller
  • , Genta Nagae
  • , Adnan M. Nagrial
  • , Hardeep K. Nahal-Bose
  • , Hitoshi Nakagama
  • , Hidewaki Nakagawa
  • , Hiromi Nakamura
  • , Toru Nakamura
  • , Kaoru Nakano
  • , Tannistha Nandi
  • , Jyoti Nangalia
  • , Mia Nastic
  • , Arcadi Navarro
  • , Fabio C. P. Navarro
  • , David E. Neal
  • , Gerd Nettekoven
  • , Felicity Newell
  • , Steven J. Newhouse
  • , Yulia Newton
  • , Alvin Wei Tian Ng
  • , Anthony Ng
  • , Jonathan Nicholson
  • , David Nicol
  • , Yongzhan Nie
  • , G. Petur Nielsen
  • , Morten Muhlig Nielsen
  • , Serena Nik-Zainal
  • , Michael S. Noble
  • , Katia Nones
  • , Paul A. Northcott
  • , Faiyaz Notta
  • , Brian D. O’Connor
  • , Peter O’Donnell
  • , Maria O’Donovan
  • , Sarah O’Meara
  • , Brian Patrick O’Neill
  • , J. Robert O’Neill
  • , David Ocana
  • , Angelica Ochoa
  • , Christopher Ogden
  • , Hideki Ohdan
  • , Kazuhiro Ohi
  • , Lucila Ohno-Machado
  • , Karin A. Oien
  • , Akinyemi I. Ojesina
  • , Hidenori Ojima
  • , Takuji Okusaka
  • , Larsson Omberg
  • , Choon Kiat Ong
  • , Stephan Ossowski
  • , German Ott
  • , B. F. Francis Ouellette
  • , Christine P’ng
  • , Marta Paczkowska
  • , Salvatore Paiella
  • , Chawalit Pairojkul
  • , Marina Pajic
  • , Qiang Pan-Hammarström
  • , Elli Papaemmanuil
  • , Irene Papatheodorou
  • , Nagarajan Paramasivam
  • , Ji Wan Park
  • , Joong-Won Park
  • , Keunchil Park
  • , Kiejung Park
  • , Peter J. Park
  • , Joel S. Parker
  • , Simon L. Parsons
  • , Harvey Pass
  • , Danielle Pasternack
  • , Alessandro Pastore
  • , Ann-Marie Patch
  • , Iris Pauporté
  • , Antonio Pea
  • , John V. Pearson
  • , Chandra Sekhar Pedamallu
  • , Jakob Skou Pedersen
  • , Paolo Pederzoli
  • , Nathan A. Pennell
  • , Charles M. Perou
  • , Marc D. Perry
  • , Gloria M. Petersen
  • , Nicholas Petrelli
  • , Robert Petryszak
  • , Stefan M. Pfister
  • , Mark Phillips
  • , Oriol Pich
  • , Hilda A. Pickett
  • , Todd D. Pihl
  • , Nischalan Pillay
  • , Sarah Pinder
  • , Mark Pinese
  • , Andreia V. Pinho
  • , Esa Pitkänen
  • , Xavier Pivot
  • , Elena Piñeiro-Yáñez
  • , Laura Planko
  • , Christoph Plass
  • , Paz Polak
  • , Tirso Pons
  • , Irinel Popescu
  • , Olga Potapova
  • , Aparna Prasad
  • , Shaun R. Preston
  • , Manuel Prinz
  • , Antonia L. Pritchard
  • , Stephenie D. Prokopec
  • , Elena Provenzano
  • , Xose S. Puente
  • , Sonia Puig
  • , Montserrat Puiggròs
  • , Sergio Pulido-Tamayo
  • , Gulietta M. Pupo
  • , Colin A. Purdie
  • , Michael C. Quinn
  • , Raquel Rabionet
  • , Janet S. Rader
  • , Bernhard Radlwimmer
  • , Petar Radovic
  • , Benjamin Raeder
  • , Keiran M. Raine
  • , Manasa Ramakrishna
  • , Kamna Ramakrishnan
  • , Suresh Ramalingam
  • , W. Kimryn Rathmell
  • , Tobias Rausch
  • , Guido Reifenberger
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  • , Jorge Reis-Filho
  • , Victor Reuter
  • , Iker Reyes-Salazar
  • , Matthew A. Reyna
  • , Sheila M. Reynolds
  • , Esther Rheinbay
  • , Yasser Riazalhosseini
  • , Andrea L. Richardson
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Contributions

M.G., C.J., I.L., S.G., P.A., D.R., D.G.L., P.T.S. and P.V.L. performed timing of point mutations and copy number gains. S.G. and M.G. performed qualitative timing of driver point mutations and analyses of synchronous gains, L.J. timed secondary copy number gains. I.L., T.J.M., D.R., D.G.L., D.C.W. and G.G. performed relative timing of somatic driver events and implemented integrative models. C.J., Y.R., M.G., Q.D.M. and P.V.L. performed timing of mutational signatures. M.G. performed real-time estimation of whole-genome duplication and subclonal diversification. S.G. assessed mutation rates in relapsed samples. C.J., M.G., I.L., Y.R., D.R. and P.V.L. constructed cancer timelines. M.G., C.J., I.L., S.C.D., S.G., T.J.M., Y.R., P.A., J.D., P.C.B., D.D.B., V.M., Q.D.M., P.T.S., D.C.W. and P.V.L. interpreted the results. S.C.D., I.L., J.W., A.D., I.V.-G., K. Yuan, G.M., M.P., S.M., N.D., K. Yu, S. Sengupta, K.H., M.T., J.D., D.G.L., D.R., J.L., M.C., S.C.S., Y.J., F.M., V.M., H.Z., W.W., Q.D.M., D.C.W. and P.V.L. performed subclonal architecture analysis. S.C.D., I.L., K.K., V.M., M.P., X.Y., D.G.L., S. Schumacher, R.B., M.I., M.S., D.C.W. and P.V.L. performed copy number analysis. J.W., S.C.D., I.L., K.H., D.G.L., K.K., D.R., D.C.W., Q.D.M. and P.V.L. derived a consensus of copy number analysis results. K. Yu, M.T., A.D., S.C.D., I.L., D.C.W., M.G., P.V.L., Q.D.M. and W.W. derived a consensus of subclonal architecture results. Y.F. and W.W. contributed to subclonal mutation calls. P.T.S., D.C.W. and P.V.L. coordinated the study. M.G., C.J., P.T.S., Y.R., I.L., Q.D.M., D.C.W. and P.V.L. wrote the manuscript, which all authors approved. S.C.D., I.L., M.G., C.J., K.H., M.T., J.W., A.G.D., K. Yu, S.G., Y.R. and G.M. in the PCAWG Evolution & Heterogeneity Working Group contributed equally. W.W., Q.D.M., P.T.S., D.C.W. and P.V.L. in the PCAWG Evolution & Heterogeneity Working Group jointly supervised the work.

Corresponding authors

Correspondence to Moritz Gerstung or Peter Van Loo .

Ethics declarations

Competing interests.

R.B. owns equity in Ampressa Therapeutics. G.G. receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect and POLYSOLVER. I.L. is a consultant for PACT Pharma. B.J.R. is a consultant at and has ownership interest (including stock and patents) in Medley Genomics. All other authors declare no competing interests.

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Extended data figures and tables

Extended data fig. 1 summary of all results obtained for colorectal adenocarcinoma ( n  = 60) as an example..

a , Clustered heat maps of mutational timing estimates for gained segments, per patient. Colours as indicated in main text: green represents early clonal events, purple represents late clonal. b , Relative ordering of copy number events and driver mutations across all samples. c , Distribution of mutations across early clonal, late clonal and subclonal stages, for the most common driver genes. A maximum of 10 driver genes are shown. d , Clustered mutational signature fold changes between early clonal and late clonal stages, per patient. Green and purple indicate, respectively, a signature decrease and increase in late clonal from early clonal mutations. Inactive signatures are coloured white. e , As in d but for clonal versus subclonal stages. Blue indicates a signature decrease and red an increase in subclonal from clonal mutations. f , Typical timeline of tumour development. Similar result summaries for all other cancer types can be found in the  Supplementary Information (pages 46–77).

Extended Data Fig. 2 Comparison of methods used for timing of individual copy number gains.

a , b , Pairwise comparison of the three approaches for timing individual copy number gains. c , Comparison using simulated data, showing high concordance.

Extended Data Fig. 3 Early copy number gains in brain cancers.

a , Three illustrative examples of glioblastoma with trisomy 7. The red arrow depicts the expected VAF cluster of point mutations preceding trisomy 7, which usually contains less than three SNVs. b , Distributions of the number of SNVs preceding trisomy 7 and total number of mutations on chromosome (chr) 7 in n  = 34 GBM samples with trisomy 7. c , Medulloblastoma example with isochromosome 17q. d , Distributions of SNVs on 17q in n  = 95 samples with isochromosome 17q; 74 out of 95 samples have less than 1 SNV preceding the isochromosome.

Extended Data Fig. 4 Validation of relative ordering model reconstruction based on simulated cohorts of whole-genome samples.

a , Relative ordering model (PhylogicNDT LeagueModel) results for a simulated cohort of samples ( n  = 100) from a single generalized relative order of events (with varied prevalence) showing high concordance with the true trajectory. Probability distributions show the uncertainty of timing for specific events in the cohort. b , Relative ordering model results on a simulated cohort of samples ( n  = 95) from a complex mixture of trajectories with different order of events showing high concordance with the expected average trajectory. c , Estimation of accuracy of the relative ordering model reconstruction by simulation of a set of 100 cohorts ( n (samples) = 100) with random trajectory mixtures and quantifying the distance in log odds early/late from perfect ordering. For the vast majority of events (even with low number of occurrences in the cohort), the log odds error does not exceed 1, confirming that very few events would switch between timing categories. The inset box corresponds to the first and third quartiles of the distribution, the horizontal line indicates the median and whiskers include data within 1.5× the IQR from the box. d , Simulated data show concordant timing in cohorts with WGD ( n  = 245). Exclusion of samples with WGD (right, n  = 242) introduces only a mild drop in accuracy, indicating that WGD is beneficial but not necessary for the reconstruction. Red dot = true rank. e , Estimated log odds in observed data including WGD (left, n  = 245) and without (right, n  = 242), across different mutation types. The inset box corresponds to the first and third quartiles of the distribution, the horizontal line indicates the median and whiskers include data within 1.5× the IQR from the box.

Extended Data Fig. 5 Correlation between the league model and Bradley–Terry model ordering.

Direct comparison for each tumour type of the league and Bradley–Terry models for determining the order of recurrent somatic mutations and copy number events. Axes indicate the ordered events observed in the respective tumour types. Correlation is quantified by Spearman’s rank correlation coefficient. A total of n  = 756 ordered events are shown.

Extended Data Fig. 6 Examples of mutation spectrum changes across tumour evolution.

a , Three examples of tumours with substantial changes between mutation spectra of early (top) and late (bottom) clonal time points. b , Three examples of tumours with substantial changes between mutation spectra of clonal (top) and subclonal (bottom) time points.

Extended Data Fig. 7 Overview of early-to-late clonal and clonal-to-subclonal signature changes across tumour types.

a , b , Pie charts representing signature changes per cancer type for early-to-late clonal signature changes ( a ) and clonal-to-subclonal signature changes ( b ). Signatures that decrease between early and late are coloured green; signatures that increase are purple. The size of each pie chart represents the frequency of each signature. Signatures are split into three categories: (1) clock-like, comprising the putative clock signatures 1 and 5; (2) frequent, which are signatures present in ten or more cancer types; and (3) cancer-type specific, which are in fewer than ten cancer types and are often limited to specific cohorts.

Extended Data Fig. 8 Age-dependent mutation burden and relapse samples indicate near-normal CpG>TpG mutation rate in cancer, with moderate acceleration during carcinogenesis.

a , Across all cancer samples, a predominantly linear accumulation of CpG>TpG mutations (scaled to copy number) is observed over time, as measured by the age at diagnosis. b , Cancer-specific analysis of the CpG>TpG mutation burden as a function of age at diagnosis for n  = 1,978 samples of 34 informative cancer types. The dotted line denotes the median mutations per year (that is, not offset), and shading denotes the 95% credible interval of a hierarchical Bayesian linear regression model across all data points. Slope and intercepts are drawn for each cancer type from a gamma distribution, respectively; inference was done by Hamiltonian Monte Carlo sampling. c , Maximum a posteriori estimates of rate and offset for 34 cancer types with 95% credible intervals as defined in b . d , Mutation rate inferred from cancer as in b and from selected normal tissue sequencing studies of n  = 140 normal haematopoietic stem cells, n  = 1 normal skin sample, n  = 182 samples from normal endometrium, and n  = 445 normal colonic crypts; error bars denote the 95% confidence interval. e , Median fraction of mutations attributed to linear age-dependent accumulation, based on estimates from b and the age at diagnosis for each sample. Error bars denote the 95% credible interval. f , g , CpG>TpG mutations per gigabase for ovarian cancer ( f ) and breast cancer ( g ) samples with matched primary and relapse samples. h , Increase in CpG>TpG mutation rate inferred from paired primary and relapse samples for six cancer types. Bars denote the range of the rate increase for different scenarios of copy number evolution, assuming ploidy changes have occurred prior (upper value) or posterior (lower value) to the branching between primary and relapse sample.

Extended Data Fig. 9 Real-time estimates indicate long latencies for some samples caused by the absence of early mutations.

a , Time of WGD for n  = 571 individual patients, split by tumour type with an estimated mutation rate increase of 5×, except for ovary–adenocarcinoma (7.5×) and CNS (2.5×). Error bars represent 80% confidence intervals, reflecting uncertainty stemming from the number of mutations per segment and onset of the rate increase. Box plots demarcate the quartiles and median of the distribution with whiskers indicating 5% and 95% quantiles. b , Scatter plots showing the time of diagnosis ( x axis) and inferred time of WGD ( y axis) with error bars as in a . c , Scatter plot of early (co-amplified) CpG>TpG mutations ( y axis) as a function of the mutational time estimate of WGD ( x axis). The black line denotes a nonlinear loess fit with 95% confidence interval. Colours define the cancer type as in a . d , Total CpG>TpG mutations ( y axis) as a function of the mutation time estimate of WGD ( x axis). Colours and fit as in c . Early molecular timing is thus caused by a depletion of early CpG>TpG mutations, rather than an inflation of late CpG>TpG mutations. e , Estimated median WGD latency of n  = 571 patients as in a for fixed ( x axis) versus patient specific rate increases, depending on the observed CpG>TpG mutation burden, allowing for a higher (up to 10×) mutation rate increase in samples with more mutations ( y axis). Error bars denote the IQR. f , Timing of subclonal diversification using CpG>TpG mutations in n  = 1,953 individual patients. Box plots and error bars for data points as in a . g , Comparison of the median duration of subclonal diversification per cancer type assuming branching and linear phylogenies.

Supplementary information

Supplementary information.

This file contains a more detailed description of all methods, three supplementary notes, and summary pages for each PCAWG cohort, with sample-level figures representing the results of each of the life history analyses: timing of gains, ordering of events, timing of drivers, signature changes and evolutionary timelines.

Reporting Summary

PCAWG Consortium author list: This file contains a full list of consortium members.

Source Data Fig. 1

Source data fig. 2, source data fig. 3, source data fig. 4, source data fig. 5, source data fig. 6, source data extended data fig. 3, source data extended data fig. 5, source data extended data fig. 6, source data extended data fig. 8, source data extended data fig. 9, rights and permissions.

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Gerstung, M., Jolly, C., Leshchiner, I. et al. The evolutionary history of 2,658 cancers. Nature 578 , 122–128 (2020). https://doi.org/10.1038/s41586-019-1907-7

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Published : 05 February 2020

Issue Date : 06 February 2020

DOI : https://doi.org/10.1038/s41586-019-1907-7

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Centuries of treatments

Over the centuries, people have using a wide range of things to try to cure cancer — everything from pastes, salts, teas to cauterization and more.

One milestone came in the 1700s when British surgeon Percivall Pott connected cancer to a clear environmental cause. He noticed that chimney sweeps were developing a specific type of cancer after being exposed to soot. The revelation led to a minimum age for chimney sweeps.

But this revelation only showed how one might avoid getting cancer, not how to treat or cure it.

"Cancer was a death sentence. People would not be given a long time to live," says Mariana Stern , a cancer epidemiologist at the University of Southern California.

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FDA approves first cell therapy to treat aggressive forms of melanoma

She adds that for a long time cancer was often treated with surgery. But as scientists and physicians realized that any cancer cells left behind — missed by surgery or hiding elsewhere in the body — could grow back later, they started looking for complementary treatments.

Around the turn of the 19th century, physicians discovered that radiation could treat cancer. Swedish physicians Tor Stenbeck and Tage Sjogren separately cured their respective patients of skin cancer using x-rays . Around the same time, many radiologists who used their own skin to determine proper radiation dosages developed leukemia . But in some cases, radiation could also cause it. So radiation is still used as a cancer treatment today — in a much more targeted way.

Chemotherapy came several decades later, in the mid-1900s. It gave doctors a way to kill cancer cells that surgery or radiation couldn't reach. The idea was that certain drugs targeted dividing cells — a hallmark of cancer cells.

Today, overall cancer survival is much higher than it was even a few decades ago. Given that there are over one hundred types of cancer, that success isn't across the board.

A plurality of cancers

"Each cancer type has its own unique characteristics," says Stern. "So I think the chances of finding one treatment or one way to cure what we call cancer is impossible."

Instead of a universal cure, researchers are looking to improve prevention and treatment for each type of cancer, which includes understanding how a cancer develops in the first place. Although around five to ten percent of cancers can be genetic, most come from random mutations in our genetic code that our cells don't fix. One mutation can lead to another, which can result in cancer.

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Q&a: this scientist developed a soap that could help fight skin cancer. he's 14..

"There are multiple environmental and even internal carcinogens that we're exposed [to] or that can increase the amount of mutations that we accumulate over the amount that we're already accumulating because of random chance," says Stern.

The list of carcinogens is long and includes everything from sun exposure to tobacco use, diets high in processed and red meats, being physically inactive — and even viruses and bacteria. All of these carcinogens can lead to different types of cancer, which may require different types of treatment.

But Stern says the number one carcinogen in her book isn't something anyone can control: age.

"As we age, our cells deteriorate and accumulate more mutations," says Stern. "We live so long nowadays, pretty much one in two people are going to get cancer across their lifetime."

But she adds that she doesn't want the message to sound so gloomy. "It's not like we're doomed; just because you get old, you will have cancer. I think a lot of it can be modified by paying attention to these other factors that we know cause cancer and are correlated with age because they accumulate over time."

Treating cancer today

In recent years, cancer survival has gone up — in part because researchers and clinicians are turning toward more personalized treatment approaches.

"One patient with breast cancer might be treated one way and another patient with breast cancer might be treated a completely different way based on the characteristics of that tumor," says Stern.

For example, one of those breast cancer patients may undergo a treatment originally developed for lung cancer because that's what the breast cancer tumors respond to best.

Scientists Race To Improve 'Living Drugs' To Fight Cancer

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Scientists race to improve 'living drugs' to fight cancer.

Another reason for moving toward personalized treatments is that cancer doesn't affect all people–or populations–the same. One big area of Stern's research is studying differences in cancer rates and outcomes in different Hispanic communities. Nationally, research lags for this population. The same can be said for American Indian, Alaska Native and African-American populations, which are also underrepresented in cancer studies.

"This introduces a disparity because a lot of the drug therapies have been designed among patients of European background," Stern says, and adds, "if we don't consider that, we may not be treating them with the best drugs that those tumors are going to respond to."

One exciting new treatment option involves harnessing a patient's own immune system to attack cancer cells. "This has proven to be extremely effective because our own immune system has a mechanism by which they can surveil our body," says Stern.

Even with cutting edge advancements in cancer treatment technology, Stern says treatment access is still a big problem.

"I think the main innovation that needs to happen is that there needs to be a commitment that every single cancer patient will get access to the best treatments that are available to them. And that's not happening now."

Want to hear about advances in medicine? Email the show at [email protected] .

Listen to Short Wave on Spotify , Apple Podcasts and Google Podcasts .

Listen to every episode of Short Wave sponsor-free and support our work at NPR by signing up for Short Wave+ at plus.npr.org/shortwave .

This episode was produced by Berly McCoy, edited by Rebecca Ramirez and fact checked by Brit Hanson. Gilly Moon was the audio engineer.

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  • v.13(6); 2021 Jun

A History of Cancer Research: Tumor Viruses

Early studies of transmissible tumors in chickens provided evidence that viruses such as avian leukosis virus (ALV) and Rous sarcoma virus (RSV) can cause cancer in these animals. Doubts about the relevance to human tumors and failures to replicate some early work meant the field of tumor virology followed a bumpy course. Nevertheless, viruses that can cause cancers in rodents and humans were ultimately identified, and several Nobel prizes were awarded for work in this area. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the early history of tumor virus research, from some of the early false starts and debates, to discovery of reverse transcriptase, and identification of human papilloma virus (HPV) as the major cause of cervical cancer.

HERE A CHICK, THERE A CHICK

The early twentieth century witnessed the rise and ignoble fall of Fibiger's Nobel Prize–winning “discovery” of worms as a cause of cancer. But all was not rotten in the state of Denmark. Elsewhere at the University of Copenhagen, Vilhelm Ellerman and Oluf Bang were also testing whether cancer might be an infectious disease. In 1908 they published a paper entitled “Experimental Leukemia in Chickens.” They had found that leukemia, a cancer of the blood cells, could be transmitted from one bird to another by injection ( Fig. 1 ). Furthermore, the causative agent was able to pass through filters too fine to permit passage of any cells, animal or bacterial. Such filterable agents, first discovered in plants, eventually became known as viruses. Ellermann and Bang had discovered avian leukosis virus (ALV), the first known tumor virus. For reasons that remain unclear, their work did not attract the attention it deserved. One criticism was that although one could transmit this leukemia by injection, there was no observable transmission from bird to bird in the absence of injection. Furthermore, not every injected animal developed the disease (∼40%), and those that did often took a while to do so (6–12 mo). There was also a concern that the increased number of white blood cells might be a physiological response to infection, rather than a true malignant proliferation. Finally, it was not then widely accepted that animals, particularly non-mammals, were good models for human disease.

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Ellermann and Bang's drawings of normal chicken bone marrow ( left ) and leukemic chicken bone marrow ( right ). The normal marrow contains dense, dark trabeculae of bone. The cells in the spaces between trabeculae are nucleated erythrocytes (red blood cells). The leukemic marrow contains little bone, many immature leukocytes (white blood cells, later shown to be B lymphocytes), and very few erythrocytes. (Reprinted from Ellermann V, Bang O. 1909. Z Hygeine Infektionskrakheiten 63: 231–273.)

Two years after Ellermann and Bang had published their work, Peyton Rous at the Rockefeller Institute described a transmissible sarcoma in chickens ( Fig. 2 ). The original tumor “was found in a barred Plymouth Rock hen of light color and pure blood” that was brought to him by a chicken breeder. Rous minced the tumor into small pieces, injected part into the other breast of the same chicken and part into two other chickens of the same brood. The original chicken died of widespread cancer 35 d later. By this time, one of the other injected chickens had also developed a palpable tumor. In his initial report Rous noted, “The tumor is at best so difficult of propagation that no attempts have been made to determine whether it can be transmitted by cell-fragments, or by cell-free derivatives.”

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The origins of Rous sarcoma virus. ( Top ) A sarcoma caused by injection of fragments of the transmissible tumor. ( Bottom ) Histopathologic evidence of a sarcoma invading into muscle. (Reprinted from Rous P. 1910. J Exp Med 12: 696–705.)

However, within a year Rous had found that by passage from chicken to chicken, the transmissible tumor had become increasingly aggressive and was now capable of metastasizing. By 1911 he was able to follow in the footsteps of Bang and Ellermann and transmit this cancer by a filterable agent. This virus eventually became known as Rous sarcoma virus (RSV). As before, the work was not generally accepted as proof that cancer could be caused by an infectious agent. On the contrary, physicians were spending considerable time and effort trying to disabuse the public of the view that human cancer was infectious. This mistaken belief often resulted in the shunning or even the quarantine of patients afflicted with cancer. In search of better career prospects, Rous stopped working on RSV a few short years after publishing his landmark paper in 1911.

Extracts of chicken tumors from Rous's laboratory did make it across the pond to England, only to become entangled in a rather Dickensian tale. It began with an unusual proposition made to a studious railway stationmaster named William Bullock. If Bullock would agree to take a wealthy but childless benefactor's name, he would be left a small fortune with which he could attend medical school. Thus, was he reborn as William Gye. He enrolled at Edinburgh University, pursued a career in cancer research, and eventually was able to repeat the experiments of Rous. Taking things one step further, he then found that he could amplify the infectious material in vitro using fragments of chicken embryos. He also claimed to have isolated similar infectious agents in tumors from mice, from rats, and from humans, all of which could cause tumors in chickens.

Gye then collaborated with J.E. Barnard, a wealthy hatter and amateur microscopist, to obtain what they believed were images of the infectious cancer virus particles. These studies were published in 1925 as back-to-back papers in The Lancet . Not surprisingly, this work attracted wide attention in the popular press, helping to again fuel fears about the infectious nature of human cancer. Ultimately, none of this work stood the test of time, except for Gye's replication of Rous's work on chicken viruses. Gye went on to become a very successful cancer research administrator, eventually serving as the Director of the Imperial Cancer Research Fund Laboratories at Mill Hill.

The field of tumor virology itself also followed a rather bumpy course. Although additional tumor viruses were isolated from chickens in Japan and elsewhere, critics harped on the lack of evidence for similar viruses in mammals. In 1933 Richard Shope at the Rockefeller Institute identified a virus capable of causing papillomas (warts) in rabbits. Rous himself propagated and studied this virus for many years. A few years later John Bittner discovered a transmissible mammary cancer in mice that was caused by a milk-borne virus that became known as mouse mammary tumor virus (MMTV). In the early 1950s, Ludwik Gross identified two more mouse tumor viruses, a murine leukemia virus and a polyoma virus, which caused many different types of cancer. Tumor viruses were then identified in a variety of other mammals, including rats, cats, cows, and monkeys.

An adenovirus isolated from human tissue was shown to cause cancer in rodents in 1962, but was ultimately found not to be a cause of human cancer. Simian vacuolating virus 40 (SV40), a contaminant discovered in cells used to produce polio vaccine, was also shown to cause cancer in rodents in 1962. However, there has been a lack of convincing evidence that SV40 causes human cancer, despite much effort.

Finally, in 1964 Michael Epstein and Yvonne Barr published evidence of the first human tumor virus. They had discovered a herpes-like virus in the lymphoblasts of patients with Burkitt's lymphoma, a cancer endemic in children in tropical Africa. Epstein–Barr virus was later shown to cause both mononucleosis (a benign proliferation of B lymphocytes) and a form of nasopharyngeal cancer endemic in certain regions of China. On the heels of the discovery of the first human tumor virus, Rous was finally awarded the Nobel Prize in Physiology or Medicine in 1966 for his discovery of a chicken sarcoma virus 55 years earlier.

THE HUMAN CONDITION

Rising political pressure in the 1970s caused President Richard Nixon to announce a “war on cancer.” Ironically, much of this pressure came from Mary Lasker, a champion of medical research whose husband Albert Lasker had created advertising campaigns that greatly increased the popularity of cigarettes ( Fig. 3 ). Viruses turned out to be important causes of cancer in domesticated animals, such as chickens, laboratory mice, house cats, and cattle. However, despite the expenditure of much effort and many dollars, viruses were not found to cause the majority of human cancers. There were a number of highly publicized false leads, derisively referred to as “rumor viruses.” These reports were most often a result of contamination of human cells by animal viruses in the laboratory. The Special Virus Cancer Program, a directed medical research effort within the National Cancer Institute (NCI), had been charged with the discovery of new human cancer viruses. The program began in 1964, grew to consume substantial resources, and was eventually discontinued in the late 1970s. In part this was due to criticism from scientists outside the walls of the NCI, who favored peer-reviewed research directed by independent individual investigators rather than a centralized bureaucracy that managed large research contracts.

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The Laskers’ contributions to cancer dissemination ( top ) and to political pressure for increasing spending on research for a cancer cure ( bottom , advertisement in The Washington Post ). ( Top , From the collection of Stanford Research Into the Impact of Tobacco Advertising [tobacco.stanford.edu]; bottom , https://profiles.nlm.nih.gov/spotlight/tl/catalog/nlm:nlmuid-101584665X20-doc .)

Eventually other human tumor viruses were discovered. Most of these viruses cause relatively rare types of cancer (e.g., HTLV-I causes lymphoid cancers of the skin; HTLV-II causes a rare form of leukemia; HHV-8 causes Kaposi's sarcoma; MCV causes Merkel cell cancer). One notable exception is a family of human papilloma viruses (HPVs) very similar to those discovered in rabbits by Shope. Two such viruses (HPV16 and HPV18) were shown by Harald zur Hausen in the 1980s to be the major cause of cancer of the uterine cervix in women. HPV also causes head and neck cancers and anogenital cancers. These observations led to a Nobel Prize in Physiology or Medicine for zur Hausen in 2008, and to the creation of preventive HPV vaccines, the first of which was approved by the FDA for clinical use in 2006.

In addition to viruses that appear to directly cause human cancer, certain viruses and other infectious agents appear to cause cancer in part via the response of the host to infection. For example, infection with hepatitis B and C viruses is strongly associated with cancer of the liver, infection with Helicobacter pylori bacteria is strongly associated with cancer of the stomach, and infection with Schistosoma haematobium is strongly associated with bladder cancer in some countries. Hepatitis B virus and H. pylori have been shown to encode proteins that can promote cell proliferation. However, these cancers all appear to require repeated cycles of infection, chronic inflammation, and tissue repair, resulting in the continued proliferation of cells that have also been exposed to environmental carcinogens. The result is an unholy alliance of three old rivals—the irritation theory, the germ theory, and the mutagen theory of cancer.

THE RISE OF THE QUANTS

In the mid-twentieth century, a number of physicists turned their attention from physics to biology. A particularly influential book called What Is Life? by Erwin Schrödinger proposed that genetic information might be contained within a chemical form. This idea spurred a group of physicists-turned-biologists to focus their attention on simpler and simpler genetic systems that could be studied by quantitative methods. The result was the Phage Group led by Max Delbrück, Alfred Hershey, and Salvador Luria. By studying the viruses of bacteria (bacteriophage or phage), they and their colleagues were able to deduce many of the basic principles of molecular biology. A by-product of their efforts was the development of methods for quantitative virology, largely based on the plaque assay first described by Félix d'Hérelle in 1917.

Similar advances in animal virology required the development of methods for studying viruses in systems simpler than a whole animal. In the early twentieth century, Alexis Carrel, a Nobel Prize–winning French surgeon, developed and publicized rather complex and somewhat mystical methods for culturing fragments of tissue in the laboratory. In 1928 Carrel reported that he could use these cultures to propagate RSV. He also claimed to have kept a continuous culture of embryonic chicken heart cells alive for decades in his laboratory at the Rockefeller Institute. His work attracted the attention of Charles “Lucky Lindy” Lindbergh, who with Carrel sought a path to physical immortality ( Fig. 4 ). Eventually Carrel's immortal chicken heart experiments failed to be repeated by others. Most likely, new cells had been continually added via the embryo extracts used to “feed” the cultures. Carrel later returned to Europe, where he became an advocate of eugenics for the Vichy government in Nazi-occupied France, thus sharing sympathies with Lindbergh.

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Charles Lindbergh, Alexis Carrel, and the quest for immortality. (Image from the National Portrait Gallery.)

The fields of animal cell culture and animal virology progressed slowly until the 1940s, when recurrent polio epidemics spurred intense interest in animal (including human) virology. In 1948, John Enders and his colleagues succeeded in propagating poliovirus in cultures of human embryonic tissue fragments. Their work led to the intensely competitive development of polio vaccines by Jonas Salk and Albert Sabin. Based on the work of Enders, in 1954 Renato Delbecco and Marguerite Vogt developed a plaque assay for poliovirus that was similar to the method used to study the viruses that had lysed bacteria. At the same time, Harry Eagle at the National Institutes of Health (NIH) was systematically determining the requirements for animal cell growth. The result was a defined medium that, when supplemented with relatively small amounts of animal serum, permitted the reproducible growth of animal cells in culture without the need for embryo extracts or plasma clots. Together these powerful methods were then applied to the quantitative study and isolation of mutants of an ever-increasing number of animal viruses, including other important human pathogens like influenza.

But what about tumor viruses? How could one study viruses that caused cells to proliferate rather than die? The key insight came from Howard Temin and Harry Rubin, a graduate student and a postdoctoral fellow working in Dulbecco's laboratory. They infected dishes of adherent fibroblasts from chicken embryos with different dilutions of RSV, layered agar over the cultures, and then watched and waited. Following infection with very dilute stocks of virus, distinct patches of transformed cells appeared ( Fig. 5 ). Normal fibroblasts are flat, spindly cells that stop proliferating once they touch one another (contact inhibition). By contrast, RSV-transformed fibroblasts round up and keep proliferating, eventually forming small mounds of cells (transformed foci) that are very refractile when seen through a phase-contrast microscope. The agar overlay was an important modification of the method described two years earlier by Manaker and Groupé, because it greatly decreased secondary foci caused by subsequent rounds of infection or by detachment and diffusion of transformed cells. Once again using the logic of the Phage School, Temin and Rubin were able to rapidly and readily quantitate stocks of a tumor virus in a far easier fashion than had been possible with assays in whole animals or chicken eggs. Temin and Rubin observed a linear relationship between the concentration of the virus and the number of foci that extended over a thousandfold range. These results implied that infection with a single viral particle was sufficient to cause the oncogenic transformation of a normal cell. Therefore, by isolating virus from a single focus formed at a low concentration of virus, one could isolate a biological clone that had arisen from a single virus particle.

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Temin and Rubin's focus assay for morphologic transformation by Rous sarcoma virus. ( Left ) Experimental scheme. ( Center ) A transformed focus visualized by phase contrast microscopy. ( Right ) Relationship between viral concentration and number of foci. ( Center and right panels from Temin H, Rubin H. 1958. Virology 6: 669–688, with permission from Elsevier.)

PROVIRAL HERESY

Temin continued these studies in his own laboratory. He noticed that some isolates of RSV transformed cells with a cobblestone-like morphology (round), whereas other isolates of RSV transformed cells with a spindly morphology (fusiform) ( Fig. 6 ). Remarkably, these characteristics bred true. Cells transformed by a “round” variant of RSV and the progeny of these cells remained “round,” as did naive cells transformed by viruses isolated from “round” cells. Similarly, cells transformed by the “fusiform” variant of RSV and the progeny of those cells remained “fusiform,” as did naive cells transformed by viruses isolated from “fusiform” cells. Furthermore, the conversion of one viral variant into another occurred very rarely, if ever. These observations led Temin to propose that the transformed state was a stably inherited property of the infected cells. To account for this heritable state, he further proposed that the genetic material of the virus somehow became part of the genetic material of the cell.

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Cells transformed by fusiform (f) variant and round (r) morphological variants of Rous sarcoma virus. (Photomicrograph by Peter Vogt from Coffin J, et al. 1997. Retroviruses . Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, with permission from Peter Vogt.)

There were precedents for viral integration into the host genome in the world of bacteriophage biology. In the 1920s, Eugene and Elizabeth Wollman at the Institut Pasteur in Paris had discovered a latent form of bacteriophage that did not cause cells to lyse. Sadly, the Wollmans were deported from France and perished in Auschwitz. After the end of World War II, their former colleague Andre Lwoff continued their work. By 1949 he had shown that some bacteriophage could exist stably within bacteria in a nonlytic (lysogenic) state. This latent form of the virus (prophage) could be inherited during bacterial division and later be re-activated to produce virus in the absence of any additional infection. Careful studies eventually showed that lysogenic bacteriophage DNA becomes integrated into the genomic DNA of infected bacteria. Much of this latter work was done by François Jacob and by Elie Wollman, the surviving son of Eugene and Elizabeth.

Temin was reportedly unaware of this work because Delbrück (with whom Elie Wollman had trained) and his colleagues at Caltech did not believe in lysogeny. However, by 1962 Vogt and Dulbecco had provided evidence via nucleic acid hybridization that polyoma, a lytic DNA tumor virus originally discovered in mice, was retained in a nonlytic form in oncogenically transformed hamster cells. Soon thereafter, Temin presented similar evidence for the incorporation of the RSV genome into infected cells, although others questioned his results. Temin's proposal that RSV becomes integrated into the DNA of an infected chicken cell genome as a provirus was met with intense skepticism for another reason.

The genome of RSV was known to be composed of RNA, not DNA. Studies of other viruses like polio and influenza had provided examples of RNA serving as a template for the production of more RNA. However, it was generally believed that the flow of information from DNA to RNA to protein was unidirectional. Temin's provirus hypothesis required the heretical conversion of viral RNA into DNA prior to integration and stable inheritance as part of host cell genomic DNA. Temin used inhibitors of DNA synthesis, RNA transcription from DNA, and protein synthesis to obtain evidence consistent with his hypothesis. Viral infection required DNA synthesis, but not protein synthesis. By contrast, viral production by infected cells required RNA synthesis but not DNA synthesis ( Fig. 7 ). Further evidence for a DNA intermediate in viral replication was provided in 1970 by the experiments of David Boettiger in the Temin laboratory. He showed that incorporation of 5-bromodeoxyuridine, a thymidine analog, into the virus caused it to become sensitive to inactivation by ultraviolet light. Similar experiments were also reported by Piero Balduzzi, John Bader, and Herbert Morgan.

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Experimental evidence for Temin's provirus hypothesis. Viral infection was prevented by inhibitors of DNA synthesis, but not inhibitors of protein synthesis. By contrast, virus production was prevented by an inhibitor of RNA transcription (actinomycin D), but not by inhibitors of DNA synthesis. (Reprinted from Temin H. 1972. Proc Natl Acad Sci 69: 1016–1020.)

Meanwhile, the criticism had been fierce and unrelenting. Michael Bishop, who would eventually propose his own controversial hypothesis about RSV, described his first encounter with Howard Temin at a scientific meeting in 1968 as follows:

The hypothesis had earned him little but ridicule and grief. So that summer evening, I watched with interest (and from a respectful distance) as Howard argued long into the night with skeptics and detractors. It was my first experience with a scientist who was essentially alone in his beliefs. What I witnessed was a lesson for a lifetime. The opposition to the provirus hypothesis that evening was strong, even vitriolic. In response, Howard was unfailingly patient and reasoned. He had no doubt that his hypothesis was correct, but he was open to constructive criticism, and he painstakingly tried to refute each opposing argument, even those that had no force other than their animus.

Eventually Temin proved to be right. In 1970 he and Satoshi Mizutani reported the existence of an enzyme within detergent-disrupted RSV virions that could indeed convert RNA into DNA. An RNA-dependent DNA polymerase was independently discovered in a murine leukemia virus by David Baltimore, a virologist who had also trained with Renato Dulbecco and was studying the mechanisms of replication of different types of animal viruses. The result was a scientific earthquake, similar in magnitude to that of New Madrid in 1812, which was said to have caused the Mississippi River to run backward. Because of the unprecedented reversal of flow of genetic information from RNA to DNA, this new viral enzyme became known as “reverse transcriptase.” The RNA tumor viruses that encode this enzyme became known as “retroviruses.”

Physical proof of the existence of a DNA provirus came shortly thereafter. Jan Svoboda, a talented virologist, had persisted in studying the biology of RSV behind the Iron Curtain in what was then Czechoslovakia. In the early 1960s he and his colleagues had been able to transform rat fibroblasts by coculture with RSV-infected chicken cells. However, the rat cells themselves were unable to produce infectious RSV unless fused to normal chicken cells. Although these findings supported the provirus theory, Temin himself remained skeptical of this evidence. In 1972, using the same methods and logic by which Oswald Avery and colleagues had first shown that DNA was the genetic material of bacteria, Miroslav Hill and Jana Hillova sealed the deal. They showed that purified genomic DNA from rat cells transformed by RSV could be introduced into uninfected chicken cells, resulting in the production of infectious RSV.

In 1975, Temin and Baltimore received a Nobel Prize in Physiology or Medicine for the discovery of reverse transcriptase, a prize they shared with their mentor Renato Dulbecco for his (and Marguerite Vogt's) work on polyomavirus. Along with the awarding of a Nobel Prize to Peyton Rous in 1966 for the discovery of RSV, this event prompted Peter Duesburg (a fellow retrovirologist) to quip, “One sick chicken, two Nobel prizes.” But that was hardly the end of the story.

From the forthcoming volume Stalking the Enemy Within: A History of Cancer Research , by Joseph Lipsick

Additional Perspectives on A History of Cancer Research available at www.cshperspectives.org

SUGGESTED READING

The phage school, cell culture, and the birth of quantitative animal virology.

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history of cancer research

A history of these pages

Cancer Research UK's About Cancer pages began life as CancerHelp UK. This was one of the first comprehensive cancer websites based in the UK. 

Our pages include information about:

  • the causes of cancer, how to reduce your risk and healthy living
  • cancer symptoms and cancer screening
  • cancer tests and treatments
  • coping with a diagnosis of cancer and the treatment side effects
  • research and clinical trials

The information is accessible, comprehensive and easy to read.

Co founders

The co founders of CancerHelp UK were Nick James and Sally Tweddle.

Nick James is a cancer specialist at the University Hospitals Birmingham NHS Foundation Trust. He is also a Professor of Oncology at the University of Birmingham Institute for Cancer Studies.

Sally Tweddle was an educationalist with an interest in literacy. Her husband's cancer and their search for cancer information online inspired CancerHelp UK.

To begin with, the Medical School server at the University of Birmingham hosted CancerHelp UK.

The management of the site passed to The Cancer Research Campaign in 2000. In 2002, The Cancer Research Campaign and the Imperial Cancer Research Fund merged. Together they formed Cancer Research UK. CancerHelp UK is now the About cancer section of Cancer Research UK's website.

Sarah Jane (Sally) Tweddle (1955–1999)

Sally was instrumental in setting up CancerHelp UK in 1994. At the time, most online cancer information was aimed at professionals. There was little information available for patients and relatives.

Sally’s background was in education. She saw how to present effective, detailed online material to the general public. The website launch was a success.

Sally earned a prestigious Fellowship in Cancer Education from the Cancer Research Campaign. In this role, she promoted the transmission of cancer information to the general public and to medical students.

Sadly, in 1999 Sally was diagnosed with a widespread cancer of the duodenum. She died peacefully at her home with her family around her, as she had wished.

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About cancer research uk's patient and health information.

The history of Cancer Research UK's patient and health information website, how the information is produced and the processes we go through to make sure our information is accurate, up-to-date and engaging.

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2002 Essays

Cancer as Metaphor: My Experiences in Basic Research 1966 - 1996.

Pollack, Robert

Driven by this dream of total victory after total war, scientists have wrapped cancer research in a variety of military metaphors over the decades. Each change in the scientific agenda of cancer research has been presented as a restatement of this war aim: to kill every last cancer cell. Untethered to the reality of cancer as avoidable, the rhetoric of cancer research has changed as well, always realigning the strategies of the cancer war with the nation's priorities. We have been through three different wars on cancer of this sort and are currently in the midst of a fourth, genetic, war today.

  • Cancer--Research
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  • Cancer--Prevention

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History of the Cancer Moonshot℠

history of cancer research

Then-Vice President Biden addresses the first meeting of the Cancer Moonshot Task Force.

During his State of the Union address on January 12, 2016, President Barack Obama announced the establishment of a Cancer Moonshot to accelerate cancer research. The effort, initially funded through the 21st Century Cures Act passed in 2016 , had the ambitious goal of making a decade's worth of progress in cancer prevention, diagnosis, and treatment in just 5 years.

White House Cancer Moonshot Task Force

President Obama appointed then Vice President Joe Biden to chair the White House Cancer Moonshot Task Force charged with producing a detailed set of findings and recommendations to:

  • accelerate our understanding of cancer and its prevention, early detection, treatment, and cure
  • improve patient access and care
  • support greater access to new research, data, and computational capabilities
  • encourage development of cancer treatments
  • identify and address any unnecessary regulatory barriers and consider ways to expedite administrative reforms
  • ensure optimal investment of federal resources
  • identify opportunities to develop public–private partnerships and increase coordination of the federal government’s efforts with the private sector, as appropriate

To ensure that the Cancer Moonshot's goals and approaches are grounded in the best science, President Obama directed the Cancer Moonshot Task Force to consult with external experts, including the presidentially appointed National Cancer Advisory Board (NCAB) . A Blue Ribbon Panel of experts was established as a working group of the NCAB to assist the board in providing this advice.

Blue Ribbon Panel

At the Blue Ribbon Panel's (BRP) first (virtual) meeting on April 11, 2016, panel members agreed to establish seven working groups to focus on major topic areas. The working groups began with broad discussions of the state of the field for their respective topics and considered more than 1,600 ideas submitted by the members and the broader cancer community at large. (Read the report about the public idea submission site .)

history of cancer research

Blue Ribbon Panel 2016 Overview

The BRP presented the working groups' recommendations in a final report to the NCAB in September 2016. Download the complete report .

The BRP report describes 10 transformative research recommendations for achieving the Cancer Moonshot's goal of making a decade's worth of progress in cancer prevention, diagnosis, and treatment in just 5 years.

  • establish a network for direct patient involvement Engage patients to contribute their comprehensive tumor profile data to expand knowledge about what therapies work, in whom, and in which types of cancer.
  • create a translational science network devoted exclusively to immunotherapy Establish a cancer immunotherapy network to discover why immunotherapy is effective in some patients but not in others.
  • develop ways to overcome cancer’s resistance to therapy Identify therapeutic targets to overcome drug resistance through studies that determine the mechanisms that lead cancer cells to become resistant to previously effective treatments.
  • build a National Cancer Data Ecosystem Create a national ecosystem for sharing and analyzing cancer data so that researchers, clinicians, and patients will be able to contribute data, which will facilitate efficient data analysis.
  • intensify research on the major drivers of childhood cancers Improve our understanding of fusion oncoproteins in pediatric cancer and use new preclinical models to develop inhibitors that target them.
  • minimize cancer treatment’s debilitating side effects Accelerate the development of guidelines for routine monitoring and management of patient-reported symptoms to minimize debilitating side effects of cancer and its treatment.
  • expand use of proven cancer prevention and early detection strategies Reduce cancer risk and cancer health disparities through approaches in development, testing, and broad adoption of proven prevention strategies.
  • mine past patient data to predict future patient outcomes Predict response to standard treatments through retrospective analysis of patient specimens.
  • develop a 3-D cancer atlas Create dynamic 3-D maps of human tumor evolution to document the genetic lesions and cellular interactions of each tumor as it evolves from a precancerous lesion to advanced cancer.
  • develop new cancer technologies Develop new enabling cancer technologies to characterize tumors and test therapies.

NCI established implementation teams that align with each of the BRP recommendations. The teams identified opportunities and developed initiatives for funding that address each of the recommendations .

Cancer Cabinet

In February 2022, President Biden kickstarted the next phase of the Cancer Moonshot with bold new goals: to reduce the cancer death rate by half within 25 years and improve the lives of people with cancer and cancer survivors.

The following month, the White House convened the Cancer Cabinet , bringing together departments and agencies from across the federal government to establish a prioritized agenda across government, including the development of new interagency programs and collaborations. The Cancer Cabinet includes members from the following executive branch departments, agencies, and offices:

  • Department of Health and Human Services
  • Department of Veterans Affairs
  • Department of Defense
  • Department of Energy
  • Department of Agriculture
  • Environmental Protection Agency
  • National Institutes of Health
  • National Cancer Institute
  • Food and Drug Administration
  • Centers for Medicare & Medicaid Services
  • Centers for Disease Control and Prevention
  • Office of Science and Technology Policy
  • Domestic Policy Council
  • Gender Policy Council
  • Office of the First Lady
  • Office of the Vice President
  • Office of Management and Budget
  • Office of Legislative Affairs
  • Office of Public Engagement
  • additional members, as needed, to help establish and make progress on Cancer Moonshot goals

Watch Now : CRI’s Patient Immunotherapy Summit

Immune to Cancer: The CRI Blog

history of cancer research

How CRI’s Immunotherapy Breakthroughs and Research are Shaping Cancer Treatment and Prevention

Today, cancer immunotherapy is the most forward-thinking and innovative form of cancer treatment for patients. Cancer immunotherapy is especially effective with treating melanoma, lung, breast, and several other types of cancer. When possible, however, there is a preferable option compared to treatment: the prevention of cancer entirely.

Want to do something big for cancer immunotherapy research? Make a donation today to the Cancer Research Institute .

CRI scientists are committed to groundbreaking cancer immunotherapy research that can benefit the lives of patients and potentially save lives. In addition to research regarding treating existing cancers, some CRI scientists are also working on forward-thinking research that can address cancer prevention and attack cancer at its roots.

CRI Scientists’ Innovative Work and Perspectives on Cancer Treatment and Prevention

1. Cancer Vaccine Discoveries

Elizabeth Jaffee, MD , deputy director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and CRI Scientific Advisory Council associate director, serves on the panel for President Joe Biden’s Cancer Moonshot Initiative . Additionally, Dr. Jaffee’s research focuses on novel cancer vaccines, and she has patents for six of them.  Dr. Jaffee foresaw the immense potential of cancer vaccines long before others did. At the 2023 CRI Patient Immunotherapy Summit , she succinctly outlined the transformative power of these vaccines.

“Vaccines are the biggest success story of the 20 th century other than penicillin,” Dr. Jaffee says. “We have suggested developing new technologies and new computational approaches that can take all of the new data we are generating and put it into a framework, biologically, that tells us which signals a tumor is sending out to cells around it to cause it to protect the tumor. Through that information we can develop drugs that can intercept those signals. We can now take vaccines, combine them with drugs, and we can make a difference. We are seeing vaccines close to approval for cancers like melanoma. We are going to see this happening more and more over the next five years.”

2. Measuring Immunotherapy Response in a Single Drop of Blood

  Valsamo (Elsa) Anagnostou, MD, PhD , director of the thoracic oncology biorepository at Johns Hopkins, leader of Precision Oncology Analytics, co-leader of the Johns Hopkins Molecular Tumor Board, co-director of the Lung Cancer Precision Medicine Center of Excellence, CRI Torrey Coast Foundation GEMINI CLIP Investigator, and CRI Clinical Accelerator is at the forefront of leveraging cutting-edge technologies to advance diagnosis and therapy response. Her pioneering work has unleashed the power of liquid biopsies to test ctDNA (circulating tumor DNA) in patient blood, revolutionizing our ability to gauge patient responses to treatment.  Liquid biopsies involve drawing small samples of blood from patients for testing. “ctDNA response is particularly informative to understand the complexity of stable disease on imaging, which represents a sizable fraction of patients in whom imaging fails to timely and accurately detect the magnitude of therapeutic response,” Dr. Anagnostou says. “ctDNA response correlated with tumor size seen on imaging, which is the gold standard for monitoring response to cancer treatments and seemed to be better correlated with survival.”

Liquid biopsies could be the first step in preventing excessive follow-up procedures and scans. This is a technology that can further be developed to test for markers in blood that can indicate presence of undetectable tumors or the presence of cancer cells even before they become large enough tumors to be detected using traditional scans.

3. The Tumor Microenvironment Holds the Answer to Cancer

Max Krummel, PhD, Robert E. Smith Endowed Chair in Experimental Pathology at the University of California San Francisco (UCSF), Professor, Department of Pathology at UCSF, and former CRI Investigator Award recipient, emphasizes the need to broaden our perspective on cancer prevention beyond the current focus on boosting T cell responses through checkpoint blockade. While acknowledging the significance of enhancing T cell activity, Dr. Krummel sees an equally promising avenue in understanding and targeting the tumor microenvironment (TME). The TME is comprised of the non-cancerous cells, blood vessels, and molecules that surround and sustain a tumor cell. He highlights, “We have started to think about the fundamental biology of the tumor and how to target [that].” This shift in focus towards comprehending the intricacies of the tumor microenvironment underscores the importance of exploring diverse approaches in our efforts to combat cancer effectively.

In the U.S. alone, about 600,000 people die from cancer annually. While treatment methods have improved in recent years, particularly with immunotherapy, there is no silver bullet for cancer prevention, there are several measures people can take to try and safeguard against a potential cancer diagnosis (via the Mayo Clinic).

Measures That can Help Prevent Cancer

1. Screen Early

Different populations are at greater risk of diagnosis depending on the type of cancer. For former and current smokers, screening against lung cancer is critical. Another example is that for women between 40-75 years old, having a mammogram every two years is greatly encouraged to guard against breast cancer .

Additionally, there are also tests that can detect specific cancer-related mutations that are routinely performed to determine if someone is at risk for cancer.

2. Limit Exposure to Harmful UV Rays

Limiting the amount of time your skin is exposed to the sun and avoiding tanning booths is a good way to safeguard against skin cancer.   If you are going to be in the sun, applying sunscreen and covering your skin as best you can be good safety measures.

3. Consider Cancer Vaccines

There are currently four distinct preventative cancer vaccines for HPV and HBV-associated cancers that have been approved by the FDA. Viral infections have proven responsible for several cancers, and preventative cancer vaccines are an important tool to help thwart off cancer before it can develop.

Additionally, there are two approved therapeutic cancer vaccines for bladder and prostate cancers. These vaccines help the immune system identify cancer cells so they can be eliminated.

4. Maintain a Healthy Diet

Certain dietary measures, such as reducing one’s intake of red meat, can help reduce an individual’s risk of a cancer diagnosis . A healthy diet is one that is focused on fruits and vegetables, while avoiding refined sugars and excess animal fat.

Between new developments in cancer immunotherapy on the horizon and greater education of the public regarding preventative measures, there is potential for a greater collective focus on cancer prevention, and therefore, a world immune to cancer.

Let's spread the word about Immunotherapy! Click to share this page with your community.

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Abstract A042: History of infertility and risk of ovarian cancer in the women’s health initiative

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Holly Harris , Kimberly Lind , Cynthia Thomson , Nazmus Saquib , Aladdin Shadyab , Peter Schnatz , Rogelio Robles-Morales , Lihong Qi , Howard Strickler , Denise Roe , Leslie Farland; Abstract A042: History of infertility and risk of ovarian cancer in the women’s health initiative. Cancer Res 1 March 2024; 84 (5_Supplement_2): A042. https://doi.org/10.1158/1538-7445.OVARIAN23-A042

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Background : Given the consistent relationship between reproductive factors (e.g. parity) and risk of epithelial ovarian cancer, several studies have investigated the relation between infertility and ovarian cancer with conflicting results. Prior research has suggested differences in risk by specific infertility subgroups, which may have contributed to the conflicting findings. Further, few studies examined associations by ovarian cancer histotypes or were able to disentangle the influence of infertility vs. fertility treatment. Differences across studies could also have been influenced by different study populations (e.g., population-based vs. clinical population/registry of in-vitro fertilization [IVF]) and lack of consistent statistical control for important confounding factors including nulliparity, number of pregnancies, and age at first pregnancy. Finally, prior prospective studies have had limited follow-up, thus not capturing cancers that occur after menopause and which may have different risk factor profiles. Our objective was to determine the association between history of infertility and risk of postmenopausal ovarian cancer in a population that had not received treatment with IVF. Methods : We utilized the Women’s Health Initiative (n=114,761) with over 25 years of follow-up. At study baseline participants were asked whether they had ever tried to become pregnant for more than one year without becoming pregnant and whether a reason was found. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of incident ovarian cancer comparing participants with a history of infertility to parous participants without infertility. Logistic regression models were used to calculate odds ratios (OR) for prevalent ovarian cancer at study baseline. Results : Approximately 16% of participants reported a history of infertility. 1,376 participants reported prevalent ovarian cancer at study baseline and 852 cases of ovarian cancer were diagnosed during study follow-up. In the prospective analyses, no statistically significant association was observed between infertility and risk of ovarian cancer overall (HR=1.16; 95% CI=0.98-1.37), by histotype, or with any specific infertility diagnoses. When prevalent ovarian cancer was examined, those reporting a history of infertility had a greater odds of ovarian cancer diagnosis (1.34; 95% CI=1.13-1.58) at WHI cohort baseline. This association was present for most infertility diagnoses with the strongest associations for hormonal/ovulatory (OR=1.97;95% CI=1.24-3.12), tubal/uterine factor (OR=1.63; 95% CI=1.15-2.31), and male factor (OR=1.71; 95% CI=1.19-2.47) infertility. Conclusions : We observed no significant association between infertility history and incident ovarian cancer in our population of postmenopausal participants. An association between infertility and ovarian cancer was present when prevalent ovarian cancer cases were examined, consistent with prior analyses that show stronger associations between ovarian cancer risk factors and ovarian cancer among younger women.

Citation Format: Holly Harris, Kimberly Lind, Cynthia Thomson, Nazmus Saquib, Aladdin Shadyab, Peter Schnatz, Rogelio Robles-Morales, Lihong Qi, Howard Strickler, Denise Roe, Leslie Farland. History of infertility and risk of ovarian cancer in the women’s health initiative [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A042.

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Women Who Changed the Face of Breast Cancer

Women Who Changed the <br> Face of Breast Cancer

March is Women’s History Month and is a time to reflect on and celebrate the women who have played and continue to play pivotal roles in American history and society. From leading advancements in science, the arts, societal change, medicine, and beyond, women have been vital forces in making America what it is today.  For a disease that affects 1 in 8 women in the United States , it is no surprise that women have been fundamental trailblazers in breast cancer study, research, support, and advocacy. This Women’s History Month, we celebrate these women and the many more who have contributed so much to the care and support of those impacted by a breast cancer diagnosis.

Important Names in Breast Cancer History

Beginning in the 1940s, each decade of American history has been marked by extraordinary accomplishments and voices of activism from women in the pursuit of supporting and improving the outcomes of those facing a breast cancer diagnosis.

Breast cancer was considered a taboo “women’s disease” in the 1940s. But thanks to vocal women who intuitively knew the importance of advocating for themselves and others, that mindset began to slowly change.

Mary Lasker

Mary Lasker

After losing a friend to cancer in 1943 and learning how little money was directed toward cancer research, Mary Lasker began advocating that more funds be directed to cancer research, leading to massive donations made to the American Cancer Society (ACS) and later to governmental funding for the National Cancer Institute (NCI). Mary’s relentless drive to invoke change and her accomplishments in advocacy and fundraising began to have an immediate impact on breast cancer patients, and began to change how women were perceived in circles of power and influence.

The 1950s saw some improvements in breast cancer treatment options, as well as the rise of women demanding better care and support during and after their breast cancer treatment.

Reach to Recovery book by Terese Lasser

Terese Lasser

After undergoing a traumatic radical mastectomy for a malignant growth in 1952, Terese Lasser was disappointed in the lack of physical and emotional follow-up care offered by her surgeon. As a result, Terese founded the Reach to Recovery program in 1954 to address issues medical professionals at the time did not feel were important, such as the stigma surrounding breast cancer, intimacy after breast cancer, physical rehabilitation, and access to prostheses, paving the way for the women’s health movement by providing social support and encouragement to women experiencing breast cancer.

The medical breakthroughs in breast cancer diagnosis and treatment of the 1960s led to many important and meaningful discoveries, some spearheaded by women in the fields of science and medicine.

Dr. Jane C. Wright with microscope

Dr. Jane C. Wright

Hailed for her pioneering work in chemotherapy —shifting it from an experimental, last-resort treatment to a more effective option—Dr. Wright, known as the “godmother of chemotherapy,” spearheaded research on the drug methotrexate to treat breast and skin cancers, paving the way for millions of cancer patients and survivors. Today, methotrexate remains one of the main chemotherapy drugs for treating breast cancer, as well as lung cancer, leukemia, and many other types of cancer.

At the culmination of her 40-year career, Dr. Wright had changed the face of chemotherapy and medicine, published a wealth of articles that continue to serve as the basis for modern cancer treatment, and established a legacy of innovation worthy of continued recognition. Read more about Dr. Wright’s incredible contributions to the field of breast cancer research in Dr. Jane C. Wright’s Powerful Legacy of Firsts .

The 1970s saw many influential and high-profile women come forward publicly to share their personal experiences with breast cancer. These women chose to share about their diagnoses through national television and print media as a way to support other breast cancer patients, raise awareness for the disease, and empower women to play active roles in their healthcare decisions.

Babette Rosmond

Babette Rosmond

Famed author and editor of Better Living and Seventeen Magazine, Babette Rosmond was diagnosed with breast cancer in 1971 after finding an olive-sized lump in her breast. Not satisfied with her first doctor’s treatment approach, Babette was vocal about her decision to seek a second opinion. Babette’s act of self-advocacy empowered women nationwide to take more active roles in their healthcare and patient-doctor relationships. 

Shirley Temple Black

Shirley Temple Black

Shirley Temple Black was diagnosed with breast cancer in 1973, a time when breast cancer was rarely discussed in public. Rather than remain silent, Shirley spoke openly about her diagnosis and mastectomy , helping other women feel comfortable to do the same. Though she was most famous for being an adored child star, Shirley used her fame to bring awareness to breast cancer and comfort to women experiencing it.

First Lady Betty Ford at the White House

First Lady Betty Ford

First Lady Betty Ford was diagnosed with breast cancer in 1974, shortly after her husband became President. The First Lady openly addressed her diagnosis and became a leading voice in the benefits of early detection . Within weeks of her diagnosis, thousands of women nationwide began visiting cancer centers for early detection screenings.

Second Lady Happy Rockefeller with husband, Vice President Nelson Rockefeller

Second Lady Happy Rockefeller

Happy Rockefeller, wife of Vice President Nelson Rockefeller, was diagnosed with breast cancer in 1974 after finding a lump in her left breast during a breast self-exam . Happy underwent a radical mastectomy of her left breast, followed by a prophylactic (preventative) mastectomy of her right breast. Happy’s experience further emphasized the importance of early detection and immediate treatment to women across the nation.

As breast cancer started to become less of a taboo topic in the 1980s, many women began advocating for themselves as survivors while encouraging and supporting other women facing disease, treatment, and survivorship.

Andre Lorde

Audre Lorde

Lauded African-American poet Audre Lorde was diagnosed with breast cancer in 1980 at the age of 44. Audre became the first woman to vocally oppose societal views that women with mastectomies should wear a prosthesis or have reconstructive surgery . Audre’s writings served as a galvanizing force to bring previously alienated survivors together in mutual support and solidarity and set the stage to make the physical realities of the disease more visible in the public eye.

As mortality rates from breast cancer began to drop in the 1990s, a testament to the increased impact of screening mammography and improved treatment for breast cancer, individuals and organizations began focusing on supporting patients at all stages of the breast cancer journey, from diagnosis through treatment and into survivorship.

Janelle Hail, NBCF Founder and CEO

Janelle Hail

After personally experiencing breast cancer in 1980, Janelle Hail committed her life to educating and advocating for women everywhere by founding National Breast Cancer Foundation (NBCF) in 1991. NBCF’s mission is to provide help and inspire hope to those affected by breast cancer through early detection , education , and support services . Because of Janelle’s determination that no one face breast cancer alone, NBCF has served over one million women since 1991 and continues to be a leading organization in breast cancer support and education.

Dr. Marisa C. Weiss

Dr. Marisa C. Weiss

Radiation oncologist Dr. Weiss was concerned about the lack of support and resources available to her cancer patients. Dr. Weiss founded Living Beyond Breast Cancer (LBBC) in 1991 to address the after-care needs of her patients. LBBC now provides trusted information and support to people nationwide who are affected by breast cancer.

history of cancer research

Evelyn Lauder

After surviving breast cancer, Evelyn Lauder founded Breast Cancer Research Foundation (BCRF) in 1993 to address the lack of funding in breast cancer research. In 1992, Evelyn co-created the signature pink ribbon and launched the first Breast Cancer Awareness campaign within the Estée Lauder company. Through her high-profile advocacy, Evelyn raised awareness by placing breast health front and center in the public eye.

Today, many women continue to advocate for advancements in breast cancer prevention, patient care, and research. The attention these women bring to the cause generates the support women need when faced with a diagnosis.

Angelina Jolie and her mother

Angelina Jolie

After losing her mother to ovarian and breast cancer, megastar Angelina Jolie tested positive for the BRCA1 gene mutation , which increases a person’s chances of developing breast cancer. In 2013, Angelina underwent a prophylactic (preventative) double mastectomy to reduce her risk of developing cancer. Her story has inspired increasing numbers of women to undergo genetic testing and preventative care, reducing their risk of breast cancer.

Joan Lunden with no hair on the cover of People Magazine

Joan Lunden

Longtime Good Morning America host Joan Lunden was diagnosed with triple negative breast cancer (TNBC) in 2014. She later learned that she had dense breast tissue , a risk factor for breast cancer. In Joan’s 2015 book, Had I Known: A Memoir of Survival, Joan wrote candidly about what she learned from her breast cancer experience, and educated women on the risks that dense breast tissue pose. An advocate for women everywhere, Joan has shared her experience with thousands nationwide, encouraging them to persevere and thrive despite a cancer diagnosis.

Those affected by breast cancer today have better access to education, treatment, and resources due to the culmination of efforts by passionate women impacted by breast cancer who were never satisfied with the status quo and who gave their expertise and voices to the ongoing quest to eradicate breast cancer. We celebrate these women and their achievements this Women’s History Month!

National Breast Cancer Foundation is here for you and your loved ones. Whether you need support, education, or help during treatment, we have a team dedicated to getting you the help you deserve.

Publish Date: February 29, 2024

Her name is Audre Lorde (AW-dree LORD; born Audrey Geraldine Lorde; February 18, 1934 – November 17, 1992) not “Andre Lorde” as you have written.

Thank you so much for bringing this to our attention. We have corrected the error.

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Home > About the AACR > History of the AACR > 115th Anniversary of the AACR > Landmarks in Cancer Research: 1961-1990

  • AACR 115th Anniversary Event
  • Landmarks in Cancer Research: Introduction
  • Landmarks in Cancer Research: 1907-1960

Landmarks in Cancer Research: 1961-1990

  • Landmarks in Cancer Research: 1991-2010
  • Landmarks in Cancer Research: 2011-Present
  • First AACR award, the G. H. A. Clowes Memorial Award, is presented to Renato Dulbecco for meritorious cancer research.
  • Triplet code for amino acid translation is deciphered. A synthetic RNA molecule consisting entirely of uracil was shown to produce a polypeptide of repeating phenylalanine amino acids. Researchers went on to show how triplets of DNA bases transcribed to RNA are then translated into the individual amino acids of peptides, with different triplets representing the different amino acids, providing the mechanism by which DNA encodes proteins. (59)

history of cancer research

  • Thelma B. Dunn ( right ) is the first woman elected as president of the AACR.
  • Epidermal growth factor discovered. A heat-stable, antigenic factor responsible for the accelerated development of the incisors and eyelids was identified (which was later called the epidermal growth factor). (60)

history of cancer research

  • Chemotherapy cures Burkitt lymphoma. The geographical distribution of Burkitt lymphoma in parts of sub-Saharan Africa, described in the early 1960s, suggested that it was caused by a vector-transmitted virus. The first successful treatment of a human cancer thought to be caused by a virus, later shown to be Epstein Barr virus, was reported. (61-64)

history of cancer research

  • RAS is identified. Research on RAS began with the first observation that a preparation of a murine leukemia virus isolated from a leukemic rat induced sarcomas in newborn rodents. (65)
  • World Medical Association adopts the Declaration of Helsinki for governing research on human subjects.
  • Seven physician members of the AACR found the American Society of Clinical Oncology (ASCO).
  • U.S. Surgeon General Luther L. Terry publicly affirms that smoking leads to lung cancer.
  • Chemoprophylaxis is demonstrated in animal models of chemical carcinogenesis. A variety of chemicals were shown to prevent cancer induced by chemicals by activating the detoxification system, competitively inhibiting the carcinogen, preventing initiation of carcinogenesis and other unknown mechanisms. The term chemoprevention was later coined as a new area of focus in cancer research. (66,67)

history of cancer research

  • Federal Cigarette Labeling and Advertising Act requires printing of warnings on cigarette packs.
  • Combination chemotherapy and maintenance treatment prolong remission. Preliminary studies of pediatric leukemia had shown synergistic effects of dual-drug treatments. By selecting agents with different side effects, it was proposed that it might be possible to combine several chemotherapy drugs to give greater efficacy without prohibitive toxicity. One of the first of these was MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine), a successful treatment for Hodgkin disease that was described in a study published in Cancer Research . Other combination chemotherapies followed. (68)

history of cancer research

  • First dedicated mammography machine is developed. For several decades prior to the invention of this machine, breast images had been obtained using standard X-ray technology. Subsequent developments allowed for reduced exposure and, eventually, digital mammograms.
  • U.S. Surgeon General requires institutional review of clinical research, leading to the establishment of institutional review boards.
  • Estrogen receptor is identified. Targets in uterine tissue were identified that interact specifically with estrogen. This finding was the first step that led to the detection of estrogen receptors in breast cancers and the design of specific and effective therapies for hormone-dependent breast cancer. (69,70)

history of cancer research

  • Rhabdomyosarcoma study leads to identification of an inherited familial cancer syndrome. A study of children with rhabdomyosarcoma who had relatives who developed other organ-site cancers at an early age led to the identification of a familial cancer syndrome, later shown to be primarily influenced by inherited mutations in p53. (71)
  • Tumors are successfully heterotransplanted into athymic “nude” mice. Heterotransplantation had only been possible in certain immuneprivileged sites in the mouse, such as the eye chamber, and eventually those grafts were rejected. The removal of the thymus, and thus the T-cell immune response, from young mice permitted transplantation of human tumors into mice for their characterization in a whole organism. (72)

history of cancer research

  • In situ hybridization is introduced. This method enabled detection of the location of specific genes within chromosomes. A wide variety of probes ranging from whole chromosome fluorescent paints to probes for individual genes and gene segments can be used to detect changes in genome copy number, structure, or nuclear location. Combining these with image analysis techniques and multiplex labeling strategies enabled multicolor cytogenetics assays termed SKY or M-FISH in which all human chromosomes can be separately visualized. (73-78)
  • Multidrug resistant cell lines are described. Resistance to multiple cytotoxic agents is one of the major causes of chemotherapy failure. Research published in Cancer Research would lead to the identification of drug transporters present in the cell membranes that control entry of drugs in and out of the cell and are important for the pharmacokinetics of drug action. (79)

history of cancer research

  • Reverse transcriptase is identified. The discovery of reverse transcriptase had implications for how viruses caused cancer and also challenged the “central dogma” that the transfer of cellular information passed from DNA to RNA to protein, and not in reverse. (80,81)

history of cancer research

  • Cell cycle is an ordered process. By fusing mammalian tissue culture cells at different stages of the cell division cycle and by observing the division of mutant yeast cells under the microscope, it was determined that the order of the cell division cycle is regulated and genes involved in cell cycle regulation were identified and ordered. This work laid the groundwork for the discovery of checkpoint proteins and how cancer cells derail checkpoints. (82-87)
  • Chromosome banding technique is developed. Q-banding using alkylating fluorochromes allowed individual chromosomes and aberrations therein to be identified with high accuracy. This technique was followed by a large number of different banding chemistries. (88,89)
  • DNA restriction enzymes are discovered. Restriction enzymes cut DNA at specific and reproducible locations.They would become an important tool in molecular biology, enabling basic characterization of genomes through early mapping techniques prior to sequencing. Once it was determined that they recognized specific sequence motifs surrounding cleavage sites, they would be used for many functions including cloning, transfer, and testing of genes and genotyping. (90)
  • U.S. Environmental Protection Agency is formed and provides regulatory enforcement against environmental carcinogens, such as asbestos.
  • The U.S. Public Health Cigarette Smoking Act bans advertisements for cigarettes.
  • Two-hit hypothesis is proposed. Using retinoblastoma as a model and observing patients with one or both eyes affected and those with and without a family history of disease, it was shown how cancer can be caused by two mutational events. In the inherited form of the disease, the first mutation or “hit” occurs in the germline cells and the second in the somatic cells. In the nonhereditary form of the cancer, both “hits” occur in somatic cells over time. (91-93)
  • Daughters of mothers who used diethylstilbestrol during pregnancy can develop vaginal cancer. Vaginal cancer is rare, particularly in young women. A small group of women ages 14 to 25 with vaginal cancer showed a highly significant association with treatment of their mothers during the first trimester of pregnancy with diethylstilbestrol (DES). In 1971, FDA issued a warning against prescribing DES for pregnant women. Between the time that DES was first manufactured in 1938 and the discovery of health problems in 1971, an estimated 5 to 10 million pregnant women and their children were exposed to the drug. (94)

history of cancer research

  • President Richard Nixon declares “War on Cancer” in State of the Union Address.
  • National Cancer Act of 1971 enables the NCI Director to expand and designate Cancer Centers and Comprehensive Cancer Centers. AACR leaders advocated for the passing of the Act and attended the signing at the White House.

history of cancer research

  • Tumor growth is dependent on angiogenesis. Starting from the observation that transplanted tumors that did not grow blood vessels were unable to increase in size, serial experiments demonstrated that tumors secrete factors that encourage new blood vessels to grow into and feed the tumor. Eventually, the genes for these factors would be identified and would become a target for molecular therapies. (95)

history of cancer research

  • Taxol, a natural plant product, is developed for chemotherapy. A component of the Pacific yew tree, Taxol was shown to actively inhibit leukemia cell lines in vitro. The isolated molecule was later produced by chemical synthesis, allowing the increased production necessary for it to be used as a drug treatment. Taxol was approved by FDA in 1992 for treating ovarian cancer and subsequently for breast cancer. (96,97)
  • Cells within a tumor can be differentiated into benign cells. Shown previously with teratomas (tumors that contain differentiated tissues), it was also demonstrated with squamous cell carcinomas that some cells within a tumor are capable of differentiating into benign cells incapable of forming a tumor when transplanted. This finding, which was published in Cancer Research, supported the idea of a cancer stem cell. (98)

history of cancer research

  • Bone marrow transplantation is established as a cancer treatment. Bone marrow transplants were used to replace blood cell-generating hematopoietic cells in patients with leukemia who had radiation therapy. Initially, transplants were from twin donors and later from donors matched by cell surface antigens. More recently, culturing stem cells extracted from the patient’s blood before treatment has been the method. (99,100)

history of cancer research

  • Apoptosis, programmed cell death, is triggered by cancer therapies. Apoptosis is the process of controlled destruction of unwanted cells, the opposite of cell replication. Cells exhibit characteristic stages of DNA and cytoplasmic condensation, followed by the breaking of the cell into apoptotic bodies and their degradation. Apoptosis can also be triggered by cytotoxic drugs. It would later be shown that tumors can arise from mutations in the apoptosis machinery, making cells resistant to death signals. (101)
  • Computerized axial tomography (CAT) scanner is invented. Previous imaging techniques had been unable to distinguish between tissues of similar density. The development of the CAT system, which uses a series of sectional X-rays, allowed a greater sensitivity of imaging, particularly for detecting abnormalities in soft tissue. (102)
  • Regression models and life tables are applied. The Cox regression model and its generalizations represented an important biostatistical advance with application to cancer research as well as many other areas. It affected the conceptualization of follow-up studies in a manner that led to nested case-control and case-cohort sampling methods and other applications relevant to clinical trial design. (103)

history of cancer research

  • NCI begins the Surveillance, Epidemiology and End Results (SEER) Program, a model for large-scale cancer registries worldwide.

history of cancer research

  • Errors in DNA replication are responsible for tumor oncogenesis. In a study published in Cancer Research , it was proposed that as DNA was synthesized the polymerase might make errors in which bases were incorporated either during replication or repair. These mutations might be the consequence of an error-prone polymerase or the presence of carcinogens. (104)
  • First Lady Betty Ford ( right ) undergoes a mastectomy and speaks publicly about breast cancer.

history of cancer research

  • Specific chromosome rearrangements are characteristic of types of leukemia. Cytogenetics and the evolution of molecular diagnostics for leukemia and lymphoma laid the groundwork for future targeted therapies. The Philadelphia chromosome of chronic myelogenous leukemia, with its characteristic translocation from chromosome 22 to 9, will later be shown to generate the fusion protein Bcr-Abl, against which the molecular treatment imatinib (Gleevec) acts. (105,106)
  • DNA cloning methods are developed. A method for isolating DNA fragments and introducing them into autonomously replicating bacterial plasmids provided the ability to isolate, identify, and amplify DNA fragments from any organism. The availability of pure and abundant sources of specific DNA fragments enabled the determination of the sequence of bases they contain, and the detection of mutations that cause cancer and heritable diseases. Ultimately, the ability to clone DNA was the basis for determining the sequence of the human and other genomes. (107,108)

history of cancer research

  • Method is developed to detect specific DNA fragments in mammalian genomes (Southern blotting). A method to detect unique sequence genes in complex genomes enabled more precise study of the genetic basis of inherited diseases and cancer. Modifications to the original technique made in 1979 substantially shortened the time needed to do the nucleic acid hybridization and increased the sensitivity to the point that single-copy genes in the human genome could be detected within a few days. (109)
  • Bromodeoxyuridine (BrdUrd) labeling techniques are introduced. Immunochemical techniques were developed to detect incorporation of BrdUrd labeled nucleotides. This was enabled by development of an antibody against BrdUrd labeled DNA, and later by development of a flow cytometric technique that simultaneously measured DNA content and incorporated BrdUrd. (110,111)
  • Monoclonal antibodies are produced. By fusing an antibody-deficient myeloma cell with a B cell it was possible to create a line of cells or hybridoma that would produce large quantities of identical or monoclonal antibodies that all recognize the same part of a molecule. Monoclonal antibodies are used in a wide range of applications, diagnostics as well as drug therapies such as trastuzumab (Herceptin). (112)

history of cancer research

  • Viral oncogenes exist in a related proto-oncogene form in normal cells. By using hybridization techniques (because this work occurred before the advent of DNA sequencing), researchers showed that there were forms of cancer-causing viral oncogenes in chicken cells. These were later shown in other species, including mice and humans. (113,114)
  • Combination chemotherapy regimen cures pediatric leukemia. By applying the previously proved theory of combining chemotherapies in different phases and based on different toxicities, and including radiotherapy, a regimen was developed that prolonged remission in 80% of patients with acute lymphocytic leukemia. (115,116)
  • American Cancer Society sponsors first “Great American Smokeout” to curb tobacco use.
  • Individual cells within a tumor have different potential for metastasis. Taking individual cells from a tumor and transplanting them into mice showed that not all cells are capable of forming new tumors and only some cells within a tumor may be capable of metastasis. (118)

history of cancer research

  • Tamoxifen is approved for treatment of breast cancer. This was the first “antihormone” therapeutic approved by FDA. Building on earlier work on oophorectomy and estrogen removal as a treatment for breast cancer, tamoxifen was shown to inhibit growth of mammary tumors in mice, leading to its approval for treatment of breast cancer. It was also shown that tamoxifen was a selective estrogen receptor modulator, acting in opposition to estrogen in some tissues but acting like estrogen in others. (117)

history of cancer research

  • RNA splicing is demonstrated. That the linear sequence of bases in mRNA results from transcription of a corresponding sequence of DNA had been accepted. New work, first done in viruses and later extended to the cellular genome, showed that mRNA is made from much larger precursors, from which segments are removed by a process called RNA splicing. Alternative splicing patterns are found in many genes to produce different protein products, such as in the p16-ARF locus, which encodes two important tumor suppressors. (119,120)
  • Medical magnetic resonance imaging (MRI) scanner is developed. The medical MRI allowed sensitive visualization of internal structures without the use of X-rays. MRI provides clearer and more detailed images of the soft tissue structure than other imaging methods, making it an invaluable tool in early diagnosis and evaluation of tumors. (121)
  • Inaugural AACR-Richard and Hinda Rosenthal Memorial Award, which recognizes research that has made, or promises to soon make, a notable contribution to improved clinical care in the field of cancer, is presented to Paul P. Carbone.
  • First AACR science policy committee, the Public Issues Committee, is formed.
  • DNA sequencing is developed. The introduction of DNA sequencing led to many advances. Over time, sequencing techniques have been refined and improved to use fluorescent dyes rather than radiolabeling, reduce sample volumes, increase the lengths of sequence read, and use automated robotic systems. (122,123)
  • Tobacco-specific nitrosamines are identified as carcinogenic components of cigarette smoke. Nitrosamines derived from nicotine were shown to cause cancer in animal models. These substances would later be shown to contribute to human lung and oral cancers. (124)
  • Human homolog of v-gag–myc is discovered. Using hybridization studies, the transforming sequence of the avian tumor virus MC29 was identified. This sequence was later named myc, for myelocytomatosis, a virus-induced disease. (125)

history of cancer research

  • p53 is discovered. Discovered as a cellular protein bound by the monkey oncogenic virus SV40, or as a transformation-associated protein in chemically induced tumors, p53 was originally thought to be an oncogene. Later studies showed that it is a tumor suppressor gene that is mutated in the germline of individuals with the Li-Fraumeni cancer predisposition syndrome and in 50% of diverse human tumors. (126-128)

history of cancer research

  • DNA damage products are detected in human DNA. As described in a study published in Cancer Research , DNA adducts were detected in cells incubated with the carcinogen benzo(a)pyrene. The adducts were more common in cells from older persons. The detection of DNA damage products would be useful for identification of carcinogens and in epidemiologic studies. (129-132)
  • Tyrosine phosphorylation and protein tyrosine kinases are discovered. The discovery of a new type of protein kinase that phosphorylates tyrosine residues in proteins, associated with the polyomavirus middle T antigen transforming protein and the Rous sarcoma virus v-Src oncoprotein, led to the conclusion that dysregulated tyrosine phosphorylation by an activated tyrosine kinase can cause malignant transformation. In subsequent years, inhibitors that target disease-causing tyrosine kinases would be approved for treatment. (133,134)
  • Method is developed to detect gene transcripts (Northern blotting). Identification of the RNA products of transcription is essential for addressing many biologic problems. The ability to separate RNA by size on gels, transfer it to a solid support, and then detect specific molecules by nucleic acid hybridization provided a critical technical link to enable detection of the transcripts produced by any gene. (135)
  • Method is developed to detect specific proteins (Western blotting). Establishing how particular genes elicit specific phenotypes requires detection of the protein products encoded by their transcripts. A rapid and sensitive method combining gel electrophoresis for fractionation, and electrophoretic transfer to a solid support for subsequent detection by specific antibodies, enabled this detection. Now proteins can also be detected using mass spectrometry. (136)
  • U.S. Department of Health, Education and Welfare creates The Belmont Report , ethical guidelines for research on humans.
  • Degradation of collagen in tumor environment promotes metastasis. For tumors to metastasize they must pass through the epithelial and endothelial basement membranes and gain access to the bloodstream. Studies showed that tumors secrete proteases that degrade collagen and that cell lines with the highest levels of collagenase had the highest potential for metastasis. (137)

history of cancer research

  • Prostate specific antigen is a marker for prostate cancer. The association of levels of prostate specific antigen with risk for prostate cancer—in a study published in Cancer Research —led to the first routine protein biomarker test used in cancer screening and prevention. (138)

history of cancer research

  • DNA methylation is shown to be important in cancer. Methylation of DNA can prevent a gene from being switched on. Chemotherapy drugs were shown to affect methylation and activate genes, suggesting that targeting methylation of specific genes may provide a way of controlling gene expression and lead to future therapies. It was later demonstrated that the methylation patterns of some genes were different in tumors compared with cells in the same tissue that were not part of the tumor. (139-141)
  • Inaugural Award for Outstanding Achievement in Cancer Research, which recognizes a young investigator (not more than 40 years of age) on the basis of meritorious achievement in cancer research, is presented to Malcolm A. S. Moore.
  • NCI commissions the National Research Council to review data linking diet and cancer.
  • Cell surface antigens of lymphocyte subtypes aid further classification of leukemias and lymphomas. A study published in Cancer Research described the development of monoclonal antibodies that recognized specific cell surface receptors characteristic of stages of lymphocyte differentiation. This allowed subclassification of different diseases and more accurate prognosis. (142,143)
  • Ubiquitin system for protein degradation is identified. How ubiquitin acts as a tagging system to mark proteins that need to be destroyed by the proteosome was demonstrated. Ubiquitination controls proteins involved in many fundamental cell processes important for cancer such as cell cycle, DNA repair, and apoptosis. Later work involved targeting drugs to this pathway as a mechanism to promote apoptosis. (144-146)

history of cancer research

  • First mouse embryonic stem (ES) cell line is established. This technology allows the generation of mouse embryos with directed mutations such as transgenics or knockouts. (147,148)
  • The Susan G. Komen Breast Cancer Foundation is founded.

history of cancer research

  • Proto-oncogenes are involved in cancer. Building on earlier work, research showed that the endogenous proto-oncogenes of normal cells could become mutated, becoming oncogenes and causing cancer. (149-151)
  • Inaugural Bruce F. Cain Memorial Award, for outstanding preclinical research that has implications for the improved care of cancer patients, is presented to John A. Montgomery.

history of cancer research

  • Helicobacter pylori is isolated from human stomach ulcers. Many decades previously, work had shown viruses involved in causing cancer, but it took years for it to be widely accepted that infection with H. pylori could cause stomach ulcers and that continuous infection and inflammation could result in cancer. (152)

history of cancer research

  • Human papillomavirus (HPV) is identified as the causative agent of cervical cancer. Early epidemiologic work documenting the low incidence of cervical cancer in nuns suggested that the disease might be caused by an infectious agent transmissible by sexual contact. The isolation of HPV DNA from biopsy samples identified the HPV 16 and 18 strains as highly associated with cervical cancer. This work would lead to the development of vaccines to prevent cervical cancer. (153)
  • National Academy of Sciences issues report, Diet, Nutrition and Cancer , leading NCI to introduce dietary guidelines to reduce cancer.
  • Oncogene cooperation for malignant transformation is demonstrated. The observations that normal cells required multiple genetic events to become oncogenically transformed provided a model for the molecular basis for the multistep nature of cancer. (154,155)

history of cancer research

  • Polymerase chain reaction (PCR) is developed. PCR uses a heat-stable DNA polymerase from thermophilic bacteria, allowing replication of multiple copies of a DNA sequence in vitro. This technique permitted an explosion of new methods for cloning, sequencing, and diagnostics and is used in virtually every genetics and molecular biology laboratory. (156)
  • Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) techniques are invented. These techniques, used in mass spectrometry, allow the analysis of biomolecules such as DNA, proteins, peptides, polymers, dendrimers, and sugars, which were too fragile to be analyzed by more conventional ionization methods. Much of our understanding about biomolecules is dependent on mass spectrometry. (157,158)
  • Bcl-2 links apoptosis and cancer. Links between Bcl-2 and apoptosis provided the first evidence of a role for programmed cell death in cancer development. (159-164)
  • Health Research Extension Act expands NCI mission to include research on the continuing care of patients and their families.
  • Lumpectomy is a viable alternative to mastectomy. Clinical studies showed that lumpectomy plus radiation therapy resulted in improved survival compared with radical mastectomy for women with early-stage breast cancer. (165)

history of cancer research

  • Telomerase is discovered. The mechanism of replication at the ends of chromosomes, or telomeres, had been unclear. The discovery of an enzyme capable of synthesizing telomeric DNA onto chromosome ends, thus replenishing them as cells divided, had implications for aging and cancer. (166)
  • National Coalition for Cancer Survivorship (NCCS) is founded.

history of cancer research

  • Retinoblastoma gene, RB, is identified. The retinoblastoma gene, RB, was identified in children with hereditary retinoblastoma and shown to be a tumor suppressor gene. (167)

history of cancer research

  • Her-2/neu receptor is overexpressed in some breast cancers. The growth factor receptor gene Her-2/neu was shown to be amplified in approximately 15% of stage I breast cancers. The degree of amplification is associated with decreased survival. This biomarker would later become the target of the highly successful molecular therapy, trastuzumab (Herceptin), improving survival in Her-2/neu-positive patients. (168)
  • CTLA-4 gene is discovered. A gene encoding the protein CTLA-4 was discovered in a screen for proteins likely to be involved in controlling T-cell activation. This protein went on to be the target of the first cancer immunotherapy of the type known as immune checkpoint inhibitors, which work by taking the “brakes” off the immune system. (169)
  • Technique is developed to use homologous recombination in mouse ES cells to create genetically engineered mouse strains. Technology to generate mice lacking specific genes, or containing specific mutations, has provided insights into the function of genes involved in development that underlies many inherited diseases and contributes to cancer. Generation of strains with mutations found in human cancers enables modeling of the initiation and progression of cancers in mice that resemble their human counterparts. Such models should prove useful for testing of biologically targeted therapies. (170,171)
  • AACR hosts its first Special Conference, “Gene Regulation and Cancer” (Chair: Phillip A. Sharp). This in-depth exchange of the latest developments in an emerging area set the tone for future AACR Special Conferences on focused topics, an ongoing series that contributes in a major way to advances in the field.
  • AACR launches Women in Cancer Research (WICR), a membership group within the AACR committed to recognizing women’s scientific achievements and fostering their career development and advancement in cancer research. The WICR Council acts as an advisory body to the AACR leadership on issues of concern to female investigators and is also responsible for organizing the activities of WICR through its committees.
  • Associate Membership, a new category of AACR membership for early-career scientists, is established. The Associate Member Council develops programs that address the needs of early-career scientists and acts as an advisory body to the AACR leadership on issues of concern to the next generation of cancer researchers.

history of cancer research

  • Tumor suppressor genes are mutated in cancer and are the targets of tumor viruses. Mutations in tumor suppressor genes have been shown to be responsible for several familial cancers such as retinoblastoma (RB) and Li-Fraumeni syndrome (p53); these genes are also spontaneously mutated in many types of noninherited cancer. They are also the targets of viral oncogenes such as the E1A proteins of adenovirus and E7 of HPV, which bind and inactivate RB. (172-174)
  • Adoptive transfer of tumor-infiltrating lymphocytes is first reported to cause tumor regression. Lymphocytes were extracted from melanoma tissue from 20 patients with metastatic melanoma, then expanded in vitro before being reinfused back into the patients, leading to tumor regression in 11 of the 20 individuals. (175)
  • Original innovation behind the engineering of chimeric antigen receptors on T cells is reported. In an effort to direct T cells, researchers generated a chimeric T-cell receptor, composed of its constant domain and an antibody’s variable domains, such that the chimeric receptor activates the T cell when it recognizes antigen specific to the antibody domains. This molecular innovation served as a foundation for the increasing number of FDA-approved chimeric antigen receptor T cell-based therapies. (176)
  • Americans with Disabilities Act protects cancer survivors against discrimination in the workplace.
  • AACR adds a second journal to its publishing program, Cell Growth & Differentiation (succeeded in 2002 by Molecular Cancer Research ).
  • Specific molecular alterations are correlated with stages of cancer progression. Expanding on the two-hit hypothesis of carcinogenesis in colorectal tumors, researchers showed that a number of events occurred, including activation of oncogenes and inactivation of tumor suppressor genes, totaling mutations in at least four to five genes, which influenced progression from a benign polyp to a large metastatic malignant tumor. (177)
  • BRCA1 mutations are associated with breast cancer. The identification of gene variants associated with a family history of breast cancer allowed screening of high-risk women and the choice for those with known increased risk to take preventive measures such as tamoxifen therapy or mastectomy. (178)
  • Breast and Cervical Cancer Mortality Prevention Act provides grants to improve programs for breast and cervical cancer prevention.
  • San Luis Obispo, California, becomes the first city in the world to ban smoking in all public buildings.
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Princeton engineering, celebrating black history month: computer vision to reconstruct lost history, and chemistry as ‘a beacon of hope’.

By the Office of Engineering Communications

February 26, 2024

This article is from the series Black History Month

In honor of Black History Month, Princeton Engineering spoke with Black women engineers from two generations. Corey Toler-Franklin, now an assistant professor at Barnard College and Columbia University, was the first African American to earn a Ph.D. in computer science from Princeton. Janice Kankolongo is a junior majoring in chemical and biological engineering who leads Princeton’s chapter of the National Society of Black Engineers.

For more information on Black History Month from Princeton University, please visit https://www.princeton.edu/news/2024/02/12/dean-jarretts-selections-black-history-month-plus-university-events-learning-and .

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From Pilot to Pageantry: Meet the 1st Active-Duty Miss America

Air Force 2nd Lt. Madison Marsh made big plans for herself when she was young, although she never really factored becoming Miss America into that equation. However, after a tough competition in January, Marsh became the first active-duty service member to earn the crown. The 22-year-old U.S. Air Force Academy graduate is now learning to navigate life as a military member, a cancer research scholar and a public figure.

A glamorous woman holding a bouquet of flowers poses for a photo.

An Early Eye on the Sky

Growing up, Marsh wanted to be a pilot and an astronaut, so she attended NASA's Space Camp at age 13. When she learned that she could further her ambitions by going to the Air Force Academy, she started working toward becoming a cadet, even earning her civilian pilot's license at 17 years old.

In 2018, Marsh lost her mother, Whitney, to pancreatic cancer. In her honor, the family started the Whitney Marsh Foundation, which raises funds for research and awareness to increase patients' chances of early detection. Marsh took on the role of co-founder and president.

Spotlight: Value of Service

The following year, Marsh made it to the Air Force Academy, but she initially had bouts of homesickness.

"I was struggling — being removed from my family, grieving my mom, and now I'm in a really tough military environment," she said, thinking back on her freshman year. That's when she was inspired by her cousin, who was a pageant contestant, to give pageantry a try. "I decided to take a stab at pageants to see all the different ways that it could help me."

A woman yells orders to two men crouched in a field.

Highlighting Similar Values

There are a lot of stereotypes regarding beauty pageants and the people involved in them, but Marsh said there are actually a lot of overlapping core values that pageants and the military share. 

"I realized pageants have always been about community service, leadership, resume building and public speaking, and I think that is what made me be able to be successful in the Air Force," she said.

After a lot of studying and several internships, including with NASA, Marsh graduated from the Air Force Academy in the spring of 2023 with a degree in physics. Upon her commissioning, she received a pilot's billet. But soon after, she was crowned Miss Colorado , and her career trajectory started to change.

A smiling woman shows off a purple ribbon pin on her uniform.

In September, Marsh decided to defer her pilot training to pursue a master's degree in public policy from the Harvard Kennedy School – an option made possible through the Air Force Institute of Technology's Civilian Institution Programs . She's also a graduate intern at Harvard Medical School and is working with experts from the Dana Farber Cancer Institute on early cancer detection research — continuing her work for the foundation dedicated to her mom.

In January, Marsh won the title of Miss America during the national pageant in Orlando, Florida. Between her Air Force commitment, her studies and now these public-facing duties, she's got a lot to juggle. Thankfully, the Air Force has rolled with her change of fortune and put her into a public affairs/recruiting position for the year that she is Miss America.

"The Air Force has been really, really wonderful with me," Marsh said during a USO event she attended on Capitol Hill in February. "Basically, anytime I go and do Miss America events, I'm also giving back to the Air Force to ensure people know about the message of what it means to serve as 2nd Lt. Marsh — the different ways that they can get involved in the military, whether it be in the Air Force or other branches or different jobs."

A woman high-fives a golden retriever.

Honoring Her Mother

As far as her Harvard research goes, Marsh said she's still working with her advisor and is excited about the possibility of bringing potential legislation related to their research to Capitol Hill over the next year.

Spotlight: Stars Behind the Stripes

"Now I understand the science side and [how to ask] medical professionals, 'What do you think needs to be done for patients, and how can we get that done through legislation?' Because through Harvard, even though I only got to do one semester there, I have learned that it is really easy to make bad policy," Marsh said. "I think the best way to making good policy is by intimately understanding from the source — with patients — and intimately understanding that scientifically so we're enacting it properly. Now that I have all of those communities able to give me that knowledge, I'm really excited to get to use that piece to come forward here on the Hill and maybe get some things done."

Dozens of people line up at a starting line for a foot race.

She said it's also a blessing for her to be able to share her mother's story on such a large stage.

"Losing her when she was 41 to pancreatic cancer — I want people to know her story. I want them to know the signs, the ways to get help … because I don't think we do enough for pancreatic cancer," Marsh said. "My mom was misdiagnosed when we had no cancer history in our family. She was healthy. She didn't have any of those warning signs, and she still passed away. We need to do more for our patients, and being able to have a national platform and a voice now to work with people is so important. I can't think of a better way to [showcase] the legacy of my mom."

Dispelling Misconceptions About Pageantry & Service

As the first active-duty service member to earn the Miss America crown, Marsh's national platform may help dispel the lingering assumption that military roles are too masculine for the average woman. Marsh said young women can make any position their own.

Air Force 2nd Lt. Madison Marsh, Miss America 2024, takes a photo with three young students.

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"I hope that women are able to see that they can define their own role in the military — whether they want to take it in the more feminine path or not — knowing that they are empowered to make that decision," Marsh said. "I hope young girls can see that you can lead in the military, or you can lead in a board room, in the courthouse, in medical boardrooms — whatever it might be — and you can be taken seriously. Whether I'm in a crown and sash or whether I'm in my uniform, I serve as 2nd Lt. Marsh and I serve as Miss America simultaneously, and they do not take away from one another."

When it comes to Miss America, there are several phases of competition: the public and private interviews, the talent portion, the evening gown and fitness competitions, as well as the social impact pitch. Between military fitness requirements and her work with the Whitney Marsh Foundation, the latter two weren't a problem for Marsh. For her, she said the hardest part was talent.

A glamorous woman holding a bouquet of flowers poses for a photo while confetti falls around her.

"I'm not conventionally talented. I can't fight, sing, dance or play an instrument — everyone would run off with their eyes and ears closed," she joked. "So, I did a monologue on my first solo flight. It was really nerve-wracking because I'm not trained in theater … and I knew the weight of what I had to carry in my speech — that I needed to deliver it perfectly, so I was able to carry the strength and the image of what I wanted military women to be portrayed as. So, that pressure was weighing on me backstage, and it was really scary."

For Service Members Considering Pageantry

When asked what advice she had for other active-duty women considering getting into pageantry, her answer was simple.

"Just do it," she said, mentioning all the different opportunities that have opened up for her. "Without pageants, I never would have had this giant platform for community service, and you can really do with that whatever you want. They leave it as a blank slate. … The Miss America opportunity has also enabled me to practice so much on public speaking, and that is a skill that you need throughout the military and throughout the rest of your life."

Not to mention the great scholarship opportunities.

"I received $70,000 in educational scholarships through Miss America, and I think that's such a beautiful way to open up doors for you and whatever phase of life that you're in," Marsh said. "So, I would challenge all the military women to join and do it because it's only up from here. I would love to see some more girls in uniform showing up and competing in the Miss America opportunity."

Her Air Force Future

Within five years, Marsh went from being a small-town girl to a strong, successful figure who's blazing a path in public policy, cancer research and the military. She said she's still trying to comprehend it all.

"I feel like I haven't had a moment to breathe yet to let it all sink in, but I will say I do feel very lucky. Without this opportunity, I obviously couldn't share all the wonderful things the Air Force has given me, whether it be all the opportunities at the Air Force Academy or now being an officer," she said.

A pilot stands with her arms crossed over her chest in front of a small glider aircraft.

Marsh clearly has a lot on her plate at the moment. As far as her future in the Air Force goes, she said at this point, anything is possible.

"This year has just opened up so many opportunities," she said. "The Air Force has given so much to me to let me do this year [as Miss America], and I want to make sure that I have my best skillset and training in mind with whatever job they put me in post-Harvard, because I want to ensure that I give back to them in the best way that I possibly can."

Marsh still has the option to attend undergraduate pilot training once she completes her master's degree. She could also choose to pursue one of 42 other line officer careers — the choice is hers.

Spotlight: Stars Behind the Stripes Spotlight: Stars Behind the Stripes:  https://www.defense.gov/Spotlights/Stars-Behind-the-Stripes/

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    In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the early history of tumor virus research, from some of the early false starts and debates, to discovery of reverse transcriptase, and identification of human papilloma virus (HPV) as the major cause of cervical cancer. Go to:

  21. A history of these pages

    Her husband's cancer and their search for cancer information online inspired CancerHelp UK. History. To begin with, the Medical School server at the University of Birmingham hosted CancerHelp UK. The management of the site passed to The Cancer Research Campaign in 2000. In 2002, The Cancer Research Campaign and the Imperial Cancer Research Fund ...

  22. Landmarks in Cancer Research: 1907-1960

    1916. AACR begins publishing The Journal of Cancer Research, the first English language cancer journal. Oophorectomy decreases breast cancer in mice. Removal of the ovaries from female mice of a strain with a high incidence of spontaneous breast cancer resulted in a decrease in tumors. Later work published in The Journal of Cancer Research ...

  23. Cancer as Metaphor: My Experiences in Basic Research 1966

    Driven by this dream of total victory after total war, scientists have wrapped cancer research in a variety of military metaphors over the decades. Each change in the scientific agenda of cancer research has been presented as a restatement of this war aim: to kill every last cancer cell. Untethered to the reality of cancer as avoidable, the rhetoric of cancer research has changed as well ...

  24. History of the Cancer Moonshot℠

    During his State of the Union address on January 12, 2016, President Barack Obama announced the establishment of a Cancer Moonshot to accelerate cancer research. The effort, initially funded through the 21st Century Cures Act passed in 2016, had the ambitious goal of making a decade's worth of progress in cancer prevention, diagnosis, and ...

  25. How CRI's Immunotherapy Breakthroughs and Research are Shaping Cancer

    CRI scientists are committed to groundbreaking cancer immunotherapy research that can benefit the lives of patients and potentially save lives. In addition to research regarding treating existing cancers, some CRI scientists are also working on forward-thinking research that can address cancer prevention and attack cancer at its roots.

  26. American Association for Cancer Research

    Abstract. Background: Given the consistent relationship between reproductive factors (e.g. parity) and risk of epithelial ovarian cancer, several studies have investigated the relation between infertility and ovarian cancer with conflicting results. Prior research has suggested differences in risk by specific infertility subgroups, which may have contributed to the conflicting findings ...

  27. Women Who Changed the

    Mary Lasker. After losing a friend to cancer in 1943 and learning how little money was directed toward cancer research, Mary Lasker began advocating that more funds be directed to cancer research, leading to massive donations made to the American Cancer Society (ACS) and later to governmental funding for the National Cancer Institute (NCI). Mary's relentless drive to invoke change and her ...

  28. Landmarks in Cancer Research: 1961-1990

    Prostate specific antigen is a marker for prostate cancer. The association of levels of prostate specific antigen with risk for prostate cancer—in a study published in Cancer Research —led to the first routine protein biomarker test used in cancer screening and prevention. (138) DNA methylation is shown to be important in cancer.

  29. Celebrating Black History Month: Computer vision to reconstruct lost

    In honor of Black History Month, Princeton Engineering spoke with Black women engineers from two generations. Corey Toler-Franklin, now an assistant professor at Barnard College and Columbia University, was the first African American to earn a Ph.D. in computer science from Princeton.

  30. From Pilot to Pageantry: Meet the 1st Active-Duty Miss America

    After becoming the first active-duty service member to become Miss America, Air Force 2nd Lt. Madison Marsh is learning to balance life as an airman, a cancer research scholar and a public figure.