TY - JOUR T1 - The evolutionary history of 2,658 cancers JF - bioRxiv DO - 10.1101/161562 SP - 161562 AU - Moritz Gerstung AU - Clemency Jolly AU - Ignaty Leshchiner AU - Stefan C. Dentro AU - Santiago Gonzalez AU - Daniel Rosebrock AU - Thomas J. Mitchell AU - Yulia Rubanova AU - Pavana Anur AU - Kaixian Yu AU - Maxime Tarabichi AU - Amit Deshwar AU - Jeff Wintersinger AU - Kortine Kleinheinz AU - Ignacio Vázquez-García AU - Kerstin Haase AU - Lara Jerman AU - Subhajit Sengupta AU - Geoff Macintyre AU - Salem Malikic AU - Nilgun Donmez AU - Dimitri G. Livitz AU - Marek Cmero AU - Jonas Demeulemeester AU - Steven Schumacher AU - Yu Fan AU - Xiaotong Yao AU - Juhee Lee AU - Matthias Schlesner AU - Paul C. Boutros AU - David D. Bowtell AU - Hongtu Zhu AU - Gad Getz AU - Marcin Imielinski AU - Rameen Beroukhim AU - S. Cenk Sahinalp AU - Yuan Ji AU - Martin Peifer AU - Florian Markowetz AU - Ville Mustonen AU - Ke Yuan AU - Wenyi Wang AU - Quaid D. Morris AU - Paul T. Spellman AU - David C. Wedge AU - Peter Van Loo AU - on behalf of the PCAWG Evolution and Heterogeneity Working Group AU - the PCAWG network Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/12/161562.abstract N2 - Cancer develops through a process of somatic evolution. Here, we use whole-genome sequencing of 2,778 tumour samples from 2,658 donors to reconstruct the life history, evolution of mutational processes, and driver mutation sequences of 39 cancer types. The early phases of oncogenesis are driven by point mutations in a small set of driver genes, often including biallelic inactivation of tumour suppressors. Early oncogenesis is also characterised by specific copy number gains, such as trisomy 7 in glioblastoma or isochromosome 17q in medulloblastoma. By contrast, increased genomic instability, a nearly four-fold diversification of driver genes, and an acceleration of point mutation processes are features of later stages. Copy-number alterations often occur in mitotic crises leading to simultaneous gains of multiple chromosomal segments. Timing analysis suggests that driver mutations often precede diagnosis by many years, and in some cases decades, providing a window of opportunity for early cancer detection. ER -