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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\n                    <jats:sup>3<\/jats:sup>\n                    . Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium\u00a0of the\u00a0International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)\n                    <jats:sup>4<\/jats:sup>\n                    , 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.\n                  <\/jats:p>","DOI":"10.1038\/s41586-019-1907-7","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T14:03:29Z","timestamp":1580911409000},"page":"122-128","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":974,"title":["The evolutionary history of 2,658 cancers"],"prefix":"10.1038","volume":"578","author":[{"given":"Moritz","family":"Gerstung","sequence":"first","affiliation":[]},{"given":"Clemency","family":"Jolly","sequence":"additional","affiliation":[]},{"given":"Ignaty","family":"Leshchiner","sequence":"additional","affiliation":[]},{"given":"Stefan C.","family":"Dentro","sequence":"additional","affiliation":[]},{"given":"Santiago","family":"Gonzalez","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Rosebrock","sequence":"additional","affiliation":[]},{"given":"Thomas J.","family":"Mitchell","sequence":"additional","affiliation":[]},{"given":"Yulia","family":"Rubanova","sequence":"additional","affiliation":[]},{"given":"Pavana","family":"Anur","sequence":"additional","affiliation":[]},{"given":"Kaixian","family":"Yu","sequence":"additional","affiliation":[]},{"given":"Maxime","family":"Tarabichi","sequence":"additional","affiliation":[]},{"given":"Amit","family":"Deshwar","sequence":"additional","affiliation":[]},{"given":"Jeff","family":"Wintersinger","sequence":"additional","affiliation":[]},{"given":"Kortine","family":"Kleinheinz","sequence":"additional","affiliation":[]},{"given":"Ignacio","family":"V\u00e1zquez-Garc\u00eda","sequence":"additional","affiliation":[]},{"given":"Kerstin","family":"Haase","sequence":"additional","affiliation":[]},{"given":"Lara","family":"Jerman","sequence":"additional","affiliation":[]},{"given":"Subhajit","family":"Sengupta","sequence":"additional","affiliation":[]},{"given":"Geoff","family":"Macintyre","sequence":"additional","affiliation":[]},{"given":"Salem","family":"Malikic","sequence":"additional","affiliation":[]},{"given":"Nilgun","family":"Donmez","sequence":"additional","affiliation":[]},{"given":"Dimitri G.","family":"Livitz","sequence":"additional","affiliation":[]},{"given":"Marek","family":"Cmero","sequence":"additional","affiliation":[]},{"given":"Jonas","family":"Demeulemeester","sequence":"additional","affiliation":[]},{"given":"Steven","family":"Schumacher","sequence":"additional","affiliation":[]},{"given":"Yu","family":"Fan","sequence":"additional","affiliation":[]},{"given":"Xiaotong","family":"Yao","sequence":"additional","affiliation":[]},{"given":"Juhee","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Matthias","family":"Schlesner","sequence":"additional","affiliation":[]},{"given":"Paul C.","family":"Boutros","sequence":"additional","affiliation":[]},{"given":"David D.","family":"Bowtell","sequence":"additional","affiliation":[]},{"given":"Hongtu","family":"Zhu","sequence":"additional","affiliation":[]},{"given":"Gad","family":"Getz","sequence":"additional","affiliation":[]},{"given":"Marcin","family":"Imielinski","sequence":"additional","affiliation":[]},{"given":"Rameen","family":"Beroukhim","sequence":"additional","affiliation":[]},{"given":"S. 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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\u00a0for PACT Pharma. B.J.R. is a consultant at and has ownership interest (including stock and\u00a0patents) in Medley Genomics.\u00a0All other authors\u00a0declare\u00a0no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}