000177478 001__ 177478 000177478 005__ 20240320145808.0 000177478 0247_ $$2doi$$a10.1038/s41586-020-1943-3 000177478 0247_ $$2pmid$$apmid:32025018 000177478 0247_ $$2pmc$$apmc:PMC7054213 000177478 0247_ $$2ISSN$$a0028-0836 000177478 0247_ $$2ISSN$$a1476-4687 000177478 0247_ $$2altmetric$$aaltmetric:75074078 000177478 037__ $$aDKFZ-2021-02565 000177478 041__ $$aEnglish 000177478 082__ $$a500 000177478 1001_ $$aAlexandrov, Ludmil B$$b0 000177478 245__ $$aThe repertoire of mutational signatures in human cancer. 000177478 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2020 000177478 3367_ $$2DRIVER$$aarticle 000177478 3367_ $$2DataCite$$aOutput Types/Journal article 000177478 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1710943033_32161 000177478 3367_ $$2BibTeX$$aARTICLE 000177478 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000177478 3367_ $$00$$2EndNote$$aJournal Article 000177478 500__ $$asiehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium;https://inrepo02.dkfz.de/record/265690 / https://doi.org/10.1038/s41586-022-05600-5 000177478 520__ $$aSomatic 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. 000177478 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000177478 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de 000177478 650_2 $$2MeSH$$aAge Factors 000177478 650_2 $$2MeSH$$aBase Sequence 000177478 650_2 $$2MeSH$$aExome: genetics 000177478 650_2 $$2MeSH$$aGenome, Human: genetics 000177478 650_2 $$2MeSH$$aHumans 000177478 650_2 $$2MeSH$$aMutation: genetics 000177478 650_2 $$2MeSH$$aNeoplasms: genetics 000177478 650_2 $$2MeSH$$aSequence Analysis, DNA 000177478 7001_ $$aKim, Jaegil$$b1 000177478 7001_ $$aHaradhvala, Nicholas J$$b2 000177478 7001_ $$aHuang, Mi Ni$$b3 000177478 7001_ $$aTian Ng, Alvin Wei$$b4 000177478 7001_ $$aWu, Yang$$b5 000177478 7001_ $$aBoot, Arnoud$$b6 000177478 7001_ $$aCovington, Kyle R$$b7 000177478 7001_ $$aGordenin, Dmitry A$$b8 000177478 7001_ $$aBergstrom, Erik N$$b9 000177478 7001_ $$aIslam, S M Ashiqul$$b10 000177478 7001_ $$aLopez-Bigas, Nuria$$b11 000177478 7001_ $$aKlimczak, Leszek J$$b12 000177478 7001_ $$aMcPherson, John R$$b13 000177478 7001_ $$aMorganella, Sandro$$b14 000177478 7001_ $$aSabarinathan, Radhakrishnan$$b15 000177478 7001_ $$aWheeler, David A$$b16 000177478 7001_ $$aMustonen, Ville$$b17 000177478 7001_ $$0P:(DE-HGF)0$$aPCAWGMutationalSignaturesWorkingGroup$$b18 000177478 7001_ $$aGetz, Gad$$b19 000177478 7001_ $$aRozen, Steven G$$b20 000177478 7001_ $$aStratton, Michael R$$b21 000177478 7001_ $$0P:(DE-HGF)0$$aPCAWGConsortium$$b22 000177478 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/s41586-020-1943-3$$gVol. 578, no. 7793, p. 94 - 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