Signatures of mutational processes in human cancer.

Nature
Authors
Keywords
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.

Year of Publication
2013
Journal
Nature
Volume
500
Issue
7463
Pages
415-21
Date Published
2013 Aug 22
ISSN
1476-4687
URL
DOI
10.1038/nature12477
PubMed ID
23945592
PubMed Central ID
PMC3776390
Links
Grant list
088340 / Wellcome Trust / United Kingdom
093867 / Wellcome Trust / United Kingdom
T32 CA009216 / CA / NCI NIH HHS / United States
098051 / Wellcome Trust / United Kingdom