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 Vázquez-García, Kerstin Haase, Lara Jerman, Subhajit Sengupta, Geoff Macintyre, Salem Malikic, Nilgun Donmez, Dimitri G. Livitz, Marek Cmero, Jonas Demeulemeester, Steven Schumacher, Yu Fan, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Paul C. Boutros, David D. Bowtell, Hongtu Zhu, Gad Getz, Marcin Imielinski, Rameen Beroukhim, S. Cenk Sahinalp, Yuan Ji, Martin Peifer, Florian Markowetz, Ville Mustonen, Ke Yuan, Wenyi Wang, Quaid D. Morris, Paul T. Spellman, David C. Wedge and Peter Loo ()
Additional contact information
Moritz Gerstung: European Bioinformatics Institute (EMBL-EBI)
Clemency Jolly: The Francis Crick Institute
Ignaty Leshchiner: Broad Institute of MIT and Harvard
Stefan C. Dentro: Wellcome Sanger Institute
Santiago Gonzalez: European Bioinformatics Institute (EMBL-EBI)
Daniel Rosebrock: Broad Institute of MIT and Harvard
Thomas J. Mitchell: Wellcome Sanger Institute
Yulia Rubanova: University of Toronto
Pavana Anur: Oregon Health & Science University
Kaixian Yu: The University of Texas MD Anderson Cancer Center
Maxime Tarabichi: Wellcome Sanger Institute
Amit Deshwar: University of Toronto
Jeff Wintersinger: University of Toronto
Kortine Kleinheinz: German Cancer Research Center (DKFZ)
Ignacio Vázquez-García: Wellcome Sanger Institute
Kerstin Haase: The Francis Crick Institute
Lara Jerman: European Bioinformatics Institute (EMBL-EBI)
Subhajit Sengupta: NorthShore University HealthSystem
Geoff Macintyre: University of Cambridge
Salem Malikic: Simon Fraser University
Nilgun Donmez: Simon Fraser University
Dimitri G. Livitz: Broad Institute of MIT and Harvard
Marek Cmero: University of Melbourne
Jonas Demeulemeester: The Francis Crick Institute
Steven Schumacher: Broad Institute of MIT and Harvard
Yu Fan: The University of Texas MD Anderson Cancer Center
Xiaotong Yao: Weill Cornell Medicine
Juhee Lee: University of California Santa Cruz
Matthias Schlesner: German Cancer Research Center (DKFZ)
Paul C. Boutros: University of Toronto
David D. Bowtell: Peter MacCallum Cancer Centre
Hongtu Zhu: The University of Texas MD Anderson Cancer Center
Gad Getz: Broad Institute of MIT and Harvard
Marcin Imielinski: Weill Cornell Medicine
Rameen Beroukhim: Broad Institute of MIT and Harvard
S. Cenk Sahinalp: Vancouver Prostate Centre
Yuan Ji: NorthShore University HealthSystem
Martin Peifer: University of Cologne
Florian Markowetz: University of Cambridge
Ville Mustonen: University of Helsinki
Ke Yuan: University of Cambridge
Wenyi Wang: The University of Texas MD Anderson Cancer Center
Quaid D. Morris: University of Toronto
Paul T. Spellman: Oregon Health & Science University
David C. Wedge: University of Oxford
Peter Loo: The Francis Crick Institute

Nature, 2020, vol. 578, issue 7793, 122-128

Abstract: 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 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.

Date: 2020
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DOI: 10.1038/s41586-019-1907-7

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