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The evolutionary history of 2,658 cancers

Author

Listed:
  • Moritz Gerstung

    (European Bioinformatics Institute (EMBL-EBI)
    Genome Biology Unit
    Wellcome Sanger Institute)

  • Clemency Jolly

    (The Francis Crick Institute)

  • Ignaty Leshchiner

    (Broad Institute of MIT and Harvard)

  • Stefan C. Dentro

    (Wellcome Sanger Institute
    The Francis Crick Institute
    University of Oxford)

  • Santiago Gonzalez

    (European Bioinformatics Institute (EMBL-EBI))

  • Daniel Rosebrock

    (Broad Institute of MIT and Harvard)

  • Thomas J. Mitchell

    (Wellcome Sanger Institute
    University of Cambridge)

  • Yulia Rubanova

    (University of Toronto
    Vector Institute)

  • Pavana Anur

    (Oregon Health & Science University)

  • Kaixian Yu

    (The University of Texas MD Anderson Cancer Center)

  • Maxime Tarabichi

    (Wellcome Sanger Institute
    The Francis Crick Institute)

  • Amit Deshwar

    (University of Toronto
    Vector Institute)

  • Jeff Wintersinger

    (University of Toronto
    Vector Institute)

  • Kortine Kleinheinz

    (German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Ignacio Vázquez-García

    (Wellcome Sanger Institute
    University of Cambridge)

  • Kerstin Haase

    (The Francis Crick Institute)

  • Lara Jerman

    (European Bioinformatics Institute (EMBL-EBI)
    University of Ljubljana)

  • Subhajit Sengupta

    (NorthShore University HealthSystem)

  • Geoff Macintyre

    (University of Cambridge)

  • Salem Malikic

    (Simon Fraser University
    Vancouver Prostate Centre)

  • Nilgun Donmez

    (Simon Fraser University
    Vancouver Prostate Centre)

  • Dimitri G. Livitz

    (Broad Institute of MIT and Harvard)

  • Marek Cmero

    (University of Melbourne
    Walter and Eliza Hall Institute)

  • Jonas Demeulemeester

    (The Francis Crick Institute
    University of Leuven)

  • Steven Schumacher

    (Broad Institute of MIT and Harvard)

  • Yu Fan

    (The University of Texas MD Anderson Cancer Center)

  • Xiaotong Yao

    (Weill Cornell Medicine
    New York Genome Center)

  • Juhee Lee

    (University of California Santa Cruz)

  • Matthias Schlesner

    (German Cancer Research Center (DKFZ))

  • Paul C. Boutros

    (University of Toronto
    Ontario Institute for Cancer Research
    University of California)

  • 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
    Massachusetts General Hospital
    Massachusetts General Hospital
    Harvard Medical School)

  • Marcin Imielinski

    (Weill Cornell Medicine
    New York Genome Center)

  • Rameen Beroukhim

    (Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute)

  • S. Cenk Sahinalp

    (Vancouver Prostate Centre
    Indiana University)

  • Yuan Ji

    (NorthShore University HealthSystem
    The University of Chicago)

  • Martin Peifer

    (University of Cologne)

  • Florian Markowetz

    (University of Cambridge)

  • Ville Mustonen

    (University of Helsinki)

  • Ke Yuan

    (University of Cambridge
    University of Glasgow)

  • Wenyi Wang

    (The University of Texas MD Anderson Cancer Center)

  • Quaid D. Morris

    (University of Toronto
    Vector Institute)

  • Paul T. Spellman

    (Oregon Health & Science University)

  • David C. Wedge

    (University of Oxford
    Oxford NIHR Biomedical Research Centre)

  • Peter Loo

    (The Francis Crick Institute
    University of Leuven)

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.

Suggested Citation

  • Moritz Gerstung & Clemency Jolly & Ignaty Leshchiner & Stefan C. Dentro & Santiago Gonzalez & Daniel Rosebrock & Thomas J. Mitchell & Yulia Rubanova & Pavana Anur & Kaixian Yu & Maxime Tarabichi & Ami, 2020. "The evolutionary history of 2,658 cancers," Nature, Nature, vol. 578(7793), pages 122-128, February.
    • Handle: RePEc:nat:nature:v:578:y:2020:i:7793:d:10.1038_s41586-019-1907-7
    DOI: 10.1038/s41586-019-1907-7
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