Gerstung, Moritz, Jolly, Clemency, Leshchiner, Ignaty, Dentro, Stefan C., Gonzalez, Santiago, Rosebrock, Daniel, Mitchell, Thomas J., Rubanova, Yulia, Anur, Pavana, Yu, Kaixian, Tarabichi, Maxime ORCID: 0000-0002-1635-2348, Deshwar, Amit, Wintersinger, Jeff, Kleinheinz, Kortine, Vazquez-Garcia, Ignacio, Haase, Kerstin ORCID: 0000-0002-0944-5618, Jerman, Lara, Sengupta, Subhajit, Macintyre, Geoff, Malikic, Salem, Donmez, Nilgun, Livitz, Dimitri G., Cmero, Marek, Demeulemeester, Jonas ORCID: 0000-0002-2660-2478, Schumacher, Steven, Fan, Yu, Yao, Xiaotong ORCID: 0000-0002-5140-6639, Lee, Juhee, Schlesner, Matthias, Boutros, Paul C., Bowtell, David D., Zhu, Hongtu, Getz, Gad, Imielinski, Marcin, Beroukhim, Rameen, Sahinalp, S. Cenk, Ji, Yuan, Peifer, Martin, Markowetz, Florian, Mustonen, Ville, Yuan, Ke, Wang, Wenyi ORCID: 0000-0003-0617-9438, Morris, Quaid D., Spellman, Paul T., Wedge, David C., Van Loo, Peter, Deshwar, Amit G., Adams, David J., Campbell, Peter J., Cao, Shaolong, Christie, Elizabeth L., Cun, Yupeng, Dawson, Kevin J., Drews, Ruben M., Eils, Roland ORCID: 0000-0002-0034-4036, Fittall, Matthew ORCID: 0000-0002-5172-4100, Garsed, Dale W., Ha, Gavin, Lee-Six, Henry, Martincorena, Inigo, Oesper, Layla, Peto, Myron, Raphael, Benjamin J., Salcedo, Adriana, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Stein, Lincoln D., Vembu, Shankar, Wheeler, David A. and Yang, Tsun-Po (2020). The evolutionary history of 2,658 cancers. Nature, 578 (7793). S. 122 - 145. BERLIN: NATURE RESEARCH. ISSN 1476-4687

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gerstung, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jolly, ClemencyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leshchiner, IgnatyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dentro, Stefan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez, SantiagoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosebrock, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, Thomas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubanova, YuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anur, PavanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, KaixianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarabichi, MaximeUNSPECIFIEDorcid.org/0000-0002-1635-2348UNSPECIFIED
Deshwar, AmitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wintersinger, JeffUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kleinheinz, KortineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vazquez-Garcia, IgnacioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haase, KerstinUNSPECIFIEDorcid.org/0000-0002-0944-5618UNSPECIFIED
Jerman, LaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sengupta, SubhajitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macintyre, GeoffUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malikic, SalemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Donmez, NilgunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Livitz, Dimitri G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cmero, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demeulemeester, JonasUNSPECIFIEDorcid.org/0000-0002-2660-2478UNSPECIFIED
Schumacher, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fan, YuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yao, XiaotongUNSPECIFIEDorcid.org/0000-0002-5140-6639UNSPECIFIED
Lee, JuheeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesner, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boutros, Paul C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bowtell, David D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, HongtuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Getz, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imielinski, MarcinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beroukhim, RameenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahinalp, S. CenkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ji, YuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Markowetz, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mustonen, VilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yuan, KeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, WenyiUNSPECIFIEDorcid.org/0000-0003-0617-9438UNSPECIFIED
Morris, Quaid D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spellman, Paul T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wedge, David C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Loo, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deshwar, Amit G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adams, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cao, ShaolongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christie, Elizabeth L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cun, YupengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dawson, Kevin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drews, Ruben M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eils, RolandUNSPECIFIEDorcid.org/0000-0002-0034-4036UNSPECIFIED
Fittall, MatthewUNSPECIFIEDorcid.org/0000-0002-5172-4100UNSPECIFIED
Garsed, Dale W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ha, GavinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee-Six, HenryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martincorena, InigoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oesper, LaylaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peto, MyronUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raphael, Benjamin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salcedo, AdrianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, RuianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shin, Seung JunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spiro, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stein, Lincoln D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vembu, ShankarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wheeler, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, Tsun-PoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-345334
DOI: 10.1038/s41586-019-1907-7
Journal or Publication Title: Nature
Volume: 578
Number: 7793
Page Range: S. 122 - 145
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATIONAL PROCESSES; BRANCHED EVOLUTION; SOMATIC MUTATION; NATURAL-HISTORY; PROGRESSION; BREAST; LANDSCAPE; SELECTION; WOMEN; SEXMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34533

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