Signatures of mutational processes in human cancer

Ludmil B. Alexandrov, Serena Nik-Zainal, David C. Wedge, Samuel A.J.R. Aparicio, Sam Behjati, Andrew V. Biankin, Graham R. Bignell, Niccolò Bolli, Ake Borg, Anne Lise Børresen-Dale, Sandrine Boyault, Birgit Burkhardt, Adam P. Butler, Carlos Caldas, Helen R. Davies, Christine Desmedt, Roland Eils, Jórunn Erla Eyfjörd, John A. Foekens, Mel GreavesFumie Hosoda, Barbara Hutter, Tomislav Ilicic, Sandrine Imbeaud, Marcin Imielinsk, Natalie Jäger, David T.W. Jones, David Jonas, Stian Knappskog, Marcel Koo, Sunil R. Lakhani, Carlos López-Otín, Sancha Martin, Nikhil C. Munshi, Hiromi Nakamura, Paul A. Northcott, Marina Pajic, Elli Papaemmanuil, Angelo Paradiso, John V. Pearson, Xose S. Puente, Keiran Raine, Manasa Ramakrishna, Andrea L. Richardson, Julia Richter, Philip Rosenstiel, Matthias Schlesner, Ton N. Schumacher, Paul N. Span, Jon W. Teague, Yasushi Totoki, Andrew N.J. Tutt, Rafael Valdés-Mas, Marit M. Van Buuren, Laura Van 'T Veer, Anne Vincent-Salomon, Nicola Waddell, Lucy R. Yates, Jessica Zucman-Rossi, P. Andrew Futreal, Ultan McDermott, Peter Lichter, Matthew Meyerson, Sean M. Grimmond, Reiner Siebert, Elías Campo, Tatsuhiro Shibata, Stefan M. Pfister, Peter J. Campbell, Michael R. Stratton

Research output: Contribution to journalArticlepeer-review

4778 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
Issue number7463
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • General


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