Journal Article

DKFZ-2020-00345

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The evolutionary history of 2,658 cancers.

Gerstung, M. ; Jolly, C. ; Leshchiner, I. ; Dentro, S. ; Gonzalez, S. ; Rosebrock, D. ; Mitchell, T. J. ; Rubanova, Y. ; Anur, P. ; Yu, K. ; Tarabichi, M. ; Deshwar, A. ; Wintersinger, J. ; Kleinheinz, K.DKFZ* ; Vázquez-García, I. ; Haase, K. ; Jerman, L. ; Sengupta, S. ; Macintyre, G. ; Malikic, S. ; Donmez, N. ; Livitz, D. G. ; Cmero, M. ; Demeulemeester, J. ; Schumacher, S. ; Fan, Y. ; Yao, X. ; Lee, J. ; Schlesner, M.DKFZ* ; Boutros, P. C. ; Bowtell, D. D. ; Zhu, H. ; Getz, G. ; Imielinski, M. ; Beroukhim, R. ; Sahinalp, S. C. ; Ji, Y. ; Peifer, M. ; Markowetz, F. ; Mustonen, V. ; Yuan, K. ; Wang, W. ; Morris, Q. D. ; PCAWGEvolution&HeterogeneityWorkingGroup ; Spellman, P. T. ; Wedge, D. C. ; Van Loo, P. ; PCAWGConsortium

2020
Nature Publ. Group52462 London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41586-019-1907-7

Abstract: Cancer develops through a process of somatic evolution1,2. 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 processes3. 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.

Note: siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium: https://inrepo02.dkfz.de/record/212474 / https://doi.org/10.1038/s41586-022-05601-4

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Contributing Institute(s):

1. Theoretische Bioinformatik (B080)
2. Bioinformatik und Omics Data Analytics (B240)
3. Epigenomik (B370)
4. Angewandte Bioinformatik (B330)
5. DKTK HD zentral (HD01)
6. B060 Molekulare Genetik (B060)
7. Pädiatrische Gliomforschung (B360)
8. DKTK Koordinierungsstelle Berlin (BE01)
9. B062 Pädiatrische Neuroonkologie (B062)
10. B066 Chromatin-Netzwerke (B066)
11. B063 Krebsgenomforschung (B063)
12. Hochdurchsatz-Sequenzierung (W190)
13. B260 Bioinformatik der Genomik und Systemgenetik (B260)
14. Core Facility Omics IT (W610)
15. B087 Neuroblastom Genomik (B087)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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