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Nature DOI:10.1038/nature12477

Signatures of mutational processes in human cancer.

Publication TypeJournal Article
Year of Publication2013
AuthorsAlexandrov, LB, Nik-Zainal, S, Wedge, DC, Aparicio, SAJR, Behjati, S, Biankin, AV, Bignell, GR, Bolli, N, Borg, A, Børresen-Dale, A-L, Boyault, S, Burkhardt, B, Butler, AP, Caldas, C, Davies, HR, Desmedt, C, Eils, R, Eyfjörd, JErla, Foekens, JA, Greaves, M, Hosoda, F, Hutter, B, Ilicic, T, Imbeaud, S, Imielinski, M, Imielinsk, M, Jäger, N, Jones, DTW, Jones, D, Knappskog, S, Kool, M, Lakhani, SR, López-Otín, C, Martin, S, Munshi, NC, Nakamura, H, Northcott, PA, Pajic, M, Papaemmanuil, E, Paradiso, A, Pearson, JV, Puente, XS, Raine, K, Ramakrishna, M, Richardson, AL, Richter, J, Rosenstiel, P, Schlesner, M, Schumacher, TN, Span, PN, Teague, JW, Totoki, Y, Tutt, ANJ, Valdés-Mas, R, van Buuren, MM, Veer, Lvan 't, Vincent-Salomon, A, Waddell, N, Yates, LR, Zucman-Rossi, J, P Futreal, A, McDermott, U, Lichter, P, Meyerson, M, Grimmond, SM, Siebert, R, Campo, E, Shibata, T, Pfister, SM, Campbell, PJ, Stratton, MR
Corporate AuthorsAustralian Pancreatic Cancer Genome Initiative, ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, ICGC PedBrain
Date Published2013 Aug 22
KeywordsAging, Algorithms, Cell Transformation, Neoplastic, Cytidine Deaminase, DNA, DNA Mutational Analysis, Humans, Models, Genetic, Mutagenesis, Mutagenesis, Insertional, Mutagens, Mutation, Neoplasms, Organ Specificity, Reproducibility of Results, Sequence Deletion, Transcription, Genetic

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.


Alternate JournalNature
PubMed ID23945592
PubMed Central IDPMC3776390
Grant List088340 / / Wellcome Trust / United Kingdom
093867 / / Wellcome Trust / United Kingdom
T32 CA009216 / CA / NCI NIH HHS / United States
098051 / / Wellcome Trust / United Kingdom