Signatures of mutational processes in human cancer
- PMID: 23945592
- PMCID: PMC3776390
- DOI: 10.1038/nature12477
Signatures of mutational processes in human cancer
Erratum in
- Nature. 2013 Oct 10;502(7470):258. Imielinsk, Marcin [corrected to Imielinski, Marcin]
Abstract
All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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Comment in
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Cancer genomics: Signature analysis suggests cancer origins.Nat Rev Genet. 2013 Oct;14(10):677. doi: 10.1038/nrg3579. Epub 2013 Aug 28. Nat Rev Genet. 2013. PMID: 23982625 No abstract available.
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Genetics: Signatures of mutational processes in cancer-a big step closer.Nat Rev Clin Oncol. 2013 Oct;10(10):545. doi: 10.1038/nrclinonc.2013.162. Epub 2013 Sep 3. Nat Rev Clin Oncol. 2013. PMID: 23999215 No abstract available.
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Genomics: Mutator catalogues.Nat Rev Cancer. 2013 Oct;13(10):681. doi: 10.1038/nrc3608. Nat Rev Cancer. 2013. PMID: 24060860 No abstract available.
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