Journal article

The evolutionary history of 2,658 cancers

Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner, Stefan C Dentro, Santiago Gonzalez, Daniel Rosebrock, Thomas J Mitchell, Yulia Rubanova, Pavana Anur, Kaixian Yu, Maxime Tarabichi, Amit Deshwar, Jeff Wintersinger, Kortine Kleinheinz, Ignacio Vazquez-Garcia, Kerstin Haase, Lara Jerman, Subhajit Sengupta, Geoff Macintyre, Salem Malikic Show all

Nature | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Cancer develops through a process of somatic evolution1,2. 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 processes3. 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 g..

View full abstract

Grants

Awarded by Francis Crick Institute from Cancer Research UK


Awarded by UK Medical Research Council


Awarded by Wellcome Trust


Awarded by Medical Research Council


Awarded by European Union


Awarded by CRUK core grants


Awarded by NIH


Awarded by US National Cancer Institute



Funding 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 Sklodowska-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.