The evolutionary history of 2,658 cancers
Thomas J. Mitchell,
Amit G. Deshwar,
Jeff A. Wintersinger,
Dimitri G Livitz,
Paul C Boutros,
David D. Bowtell,
S. Cenk Sahinalp,
Paul T Spellman,
David C Wedge,
Peter Van Loo,
on behalf of the PCAWG Evolution and Heterogeneity Working Group,
the PCAWG network
Posted 11 Jul 2017
bioRxiv DOI: 10.1101/161562 (published DOI: 10.1038/s41586-019-1907-7)
Posted 11 Jul 2017
Cancer develops through a process of somatic evolution. Here, we reconstruct the evolutionary history of 2,778 tumour samples from 2,658 donors spanning 39 cancer types. Characteristic copy number gains, such as trisomy 7 in glioblastoma or isochromosome 17q in medulloblastoma, are found amongst the earliest events in tumour evolution. The early phases of oncogenesis are driven by point mutations in a restricted set of cancer genes, often including biallelic inactivation of tumour suppressors. By contrast, increased genomic instability, a more than three-fold diversification of driver genes, and an acceleration of mutational processes are features of later stages. Clock-like mutations yield estimates for whole genome duplications and subclonal diversification in chronological time. Our results suggest that driver mutations often precede diagnosis by many years, and in some cases decades. Taken together, these data reveal common and divergent trajectories of cancer evolution, pivotal for understanding tumour biology and guiding early cancer detection.
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