The evolutionary history of 2,658 cancers

被引：679

作者：

Gerstung, Moritz ^{[1
,2
,3
]}

Jolly, Clemency ^{[4
]}

Leshchiner, Ignaty ^{[5
]}

Dentro, Stefan C. ^{[3
,4
,6
]}

Gonzalez, Santiago ^{[1
]}

Rosebrock, Daniel ^{[5
]}

Mitchell, Thomas J. ^{[3
,7
]}

Rubanova, Yulia ^{[8
,9
]}

Anur, Pavana ^{[10
]}

Yu, Kaixian ^{[11
]}

Tarabichi, Maxime ^{[3
,4
]}

Deshwar, Amit ^{[8
,9
]}

Wintersinger, Jeff ^{[8
,9
]}

Kleinheinz, Kortine ^{[12
,13
]}

Vazquez-Garcia, Ignacio ^{[3
,7
]}

Haase, Kerstin ^{[4
]}

Jerman, Lara ^{[1
,14
]}

Sengupta, Subhajit ^{[15
]}

Macintyre, Geoff ^{[16
]}

Malikic, Salem ^{[17
,18
]}

Donmez, Nilgun ^{[17
,18
]}

Livitz, Dimitri G. ^{[5
]}

Cmero, Marek ^{[19
,20
]}

Demeulemeester, Jonas ^{[4
,21
]}

Schumacher, Steven ^{[5
]}

Fan, Yu ^{[11
]}

Yao, Xiaotong ^{[22
,23
]}

Lee, Juhee ^{[24
]}

Schlesner, Matthias ^{[12
]}

Boutros, Paul C. ^{[8
,25
,26
]}

Bowtell, David D. ^{[27
]}

Zhu, Hongtu ^{[11
]}

Getz, Gad ^{[5
,28
,29
,30
]}

Imielinski, Marcin ^{[22
,23
]}

Beroukhim, Rameen ^{[5
,31
]}

Sahinalp, S. Cenk ^{[18
,32
]}

Ji, Yuan ^{[15
,33
]}

Peifer, Martin ^{[34
]}

Markowetz, Florian ^{[16
]}

Mustonen, Ville ^{[35
]}

Yuan, Ke ^{[16
,36
]}

Wang, Wenyi ^{[11
]}

Morris, Quaid D. ^{[8
,9
]}

Spellman, Paul T. ^{[10
]}

Wedge, David C. ^{[6
,37
]}

Van Loo, Peter ^{[4
,21
]}

Deshwar, Amit G. ^{[8
,9
]}

Adams, David J. ^{[3
]}

Campbell, Peter J. ^{[3
]}

Cao, Shaolong ^{[11
]}

机构：

[1] European Bioinformat Inst, European Mol Biol Lab, Cambridge, England

[2] European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany

[3] Wellcome Sanger Inst, Cambridge, England

[4] Francis Crick Inst, London, England

[5] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[6] Univ Oxford, USABig Data Inst, Oxford, England

[7] Univ Cambridge, Cambridge, England

[8] Univ Toronto, Toronto, ON, Canada

[9] Vector Inst, Toronto, ON, Canada

[10] Oregon Hlth & Sci Univ, Mol & Med Genet, Portland, OR 97201 USA

[11] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[12] German Canc Res Ctr, Heidelberg, Germany

[13] Heidelberg Univ, Heidelberg, Germany

[14] Univ Ljubljana, Ljubljana, Slovenia

[15] NorthShore Univ HealthSyst, Evanston, IL USA

[16] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England

[17] Simon Fraser Univ, Burnaby, BC, Canada

[18] Vancouver Prostate Ctr, Vancouver, BC, Canada

[19] Univ Melbourne, Melbourne, Vic, Australia

[20] Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia

[21] Univ Leuven, Leuven, Belgium

[22] Weill Cornell Med, New York, NY USA

[23] New York Genome Ctr, New York, NY USA

[24] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA

[25] Ontario Inst Canc Res, Toronto, ON, Canada

[26] Univ Calif Los Angeles, Los Angeles, CA USA

[27] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[28] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA

[29] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[30] Harvard Med Sch, Boston, MA 02115 USA

[31] Dana Farber Canc Inst, Boston, MA 02115 USA

[32] Indiana Univ, Bloomington, IN USA

[33] Univ Chicago, Chicago, IL 60637 USA

[34] Univ Cologne, Cologne, Germany

[35] Univ Helsinki, Helsinki, Finland

[36] Univ Glasgow, Glasgow, Lanark, Scotland

[37] Oxford NIHR Biomed Res Ctr, Oxford, England

[38] Carleton Coll, Dept Comp Sci, Northfield, MN 55057 USA

[39] Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA

[40] Korea Univ, Seoul, South Korea

[41] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

来源：

NATURE | 2020年 / 578卷 / 7793期

基金：

英国惠康基金; 英国医学研究理事会; 加拿大自然科学与工程研究理事会;

关键词：

MUTATIONAL PROCESSES; BRANCHED EVOLUTION; SOMATIC MUTATION; NATURAL-HISTORY; PROGRESSION; BREAST; LANDSCAPE; SELECTION; WOMEN; SEX;

D O I：

10.1038/s41586-019-1907-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cancer develops through a process of somatic evolution(1,2). 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 processes(3). 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.

引用

页码：122 / +

页数：23

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