Journal Article

DKFZ-2021-02565

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The repertoire of mutational signatures in human cancer.

Alexandrov, L. B. ; Kim, J. ; Haradhvala, N. J. ; Huang, M. N. ; Tian Ng, A. W. ; Wu, Y. ; Boot, A. ; Covington, K. R. ; Gordenin, D. A. ; Bergstrom, E. N. ; Islam, S. M. A. ; Lopez-Bigas, N. ; Klimczak, L. J. ; McPherson, J. R. ; Morganella, S. ; Sabarinathan, R. ; Wheeler, D. A. ; Mustonen, V. ; PCAWGMutationalSignaturesWorkingGroup ; Getz, G. ; Rozen, S. G. ; Stratton, M. R. ; PCAWGConsortium

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

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Please use a persistent id in citations: doi:10.1038/s41586-020-1943-3

Abstract: Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

Keyword(s): Age Factors (MeSH) ; Base Sequence (MeSH) ; Exome: genetics (MeSH) ; Genome, Human: genetics (MeSH) ; Humans (MeSH) ; Mutation: genetics (MeSH) ; Neoplasms: genetics (MeSH) ; Sequence Analysis, DNA (MeSH)

Note: siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium;https://inrepo02.dkfz.de/record/265690 / https://doi.org/10.1038/s41586-022-05600-5

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)
2. B260 Bioinformatik der Genomik und Systemgenetik (B260)
3. Angewandte Bioinformatik (B330)
4. DKTK HD zentral (HD01)
5. Pädiatrische Gliomforschung (B360)
6. Epigenomik und Krebsrisikofaktoren (C010)
7. Theoretische Bioinformatik (B080)
8. Epigenomik (B370)
9. B060 Molekulare Genetik (B060)
10. B062 Pädiatrische Neuroonkologie (B062)
11. B066 Chromatin-Netzwerke (B066)
12. Core Facility Omics IT (W610)
13. B063 Krebsgenomforschung (B063)
14. B087 Neuroblastom Genomik (B087)
15. Hochdurchsatz-Sequenzierung (W190)

Research Program(s):

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

Appears in the scientific report 2020

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; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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