RT Journal Article
SR Electronic
T1 The evolutionary history of 2,658 cancers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 161562
DO 10.1101/161562
A1 Moritz Gerstung
A1 Clemency Jolly
A1 Ignaty Leshchiner
A1 Stefan C. Dentro
A1 Santiago Gonzalez
A1 Thomas J. Mitchell
A1 Yulia Rubanova
A1 Pavana Anur
A1 Daniel Rosebrock
A1 Kaixan Yu
A1 Maxime Tarabichi
A1 Amit Deshwar
A1 Jeff Wintersinger
A1 Kortine Kleinheinz
A1 Ignacio Vázquez-García
A1 Kerstin Haase
A1 Subhajit Sengupta
A1 Geoff Macintyre
A1 Salem Malikic
A1 Nilgun Donmez
A1 Dimitri G. Livitz
A1 Marek Cmero
A1 Jonas Demeulemeester
A1 Steve Schumacher
A1 Yu Fan
A1 Xiaotong Yao
A1 Juhee Lee
A1 Matthias Schlesner
A1 Paul C. Boutros
A1 David D. Bowtell
A1 Hongtu Zhu
A1 Gad Getz
A1 Marcin Imielinski
A1 Rameen Beroukhim
A1 S. Cenk Sahinalp
A1 Yuan Ji
A1 Martin Peifer
A1 Florian Markowetz
A1 Ville Mustonen
A1 Ke Yuan
A1 Wenyi Wang
A1 Quaid D. Morris
A1 Paul T. Spellman
A1 David C. Wedge
A1 Peter Van Loo
A1 on behalf of the PCAWG Evolution and Heterogeneity Working Group
A1 the PCAWG network
A1 Stefan C. Dentro
A1 Ignaty Leshchiner
A1 Moritz Gerstung
A1 Clemency Jolly
A1 Kerstin Haase
A1 Jeff Wintersinger
A1 Pavana Anur
A1 Rameen Beroukhim
A1 Paul C. Boutros
A1 David D. Bowtell
A1 Peter J. Campbell
A1 Elizabeth L. Christie
A1 Marek Cmero
A1 Yupeng Cun
A1 Kevin Dawson
A1 Jonas Demeulemeester
A1 Amit Deshwar
A1 Nilgun Donmez
A1 Roland Eils
A1 Yu Fan
A1 Matthew Fittall
A1 Dale W. Garsed
A1 Gad Getz
A1 Santiago Gonzalez
A1 Gavin Ha
A1 Marcin Imielinski
A1 Yuan Ji
A1 Kortine Kleinheinz
A1 Juhee Lee
A1 Henry Lee-Six
A1 Dimitri G. Livitz
A1 Geoff Macintyre
A1 Salem Malikic
A1 Florian Markowetz
A1 Inigo Martincorena
A1 Thomas J. Mitchell
A1 Ville Mustonen
A1 Layla Oesper
A1 Martin Peifer
A1 Myron Peto
A1 Benjamin J. Raphael
A1 Daniel Rosebrock
A1 Yulia Rubanova
A1 S. Cenk Sahinalp
A1 Salcedo Adriana
A1 Matthias Schlesner
A1 Steve Schumacher
A1 Subhajit Sengupta
A1 Lincoln D. Stein
A1 Maxime Tarabichi
A1 Ignacio Vázquez-García
A1 Shankar Vembu
A1 Wenyi Wang
A1 David A. Wheeler
A1 Tsun-Po Yang
A1 Xiaotong Yao
A1 Fouad Yousif
A1 Kaixian Yu
A1 Ke Yuan
A1 Hongtu Zhu
A1 Quaid D. Morris
A1 Paul T. Spellman
A1 David C. Wedge
A1 Peter Van Loo
YR 2017
UL http://biorxiv.org/content/early/2017/07/11/161562.abstract
AB 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.