Signatures of mutational processes in human cancer.
Alexandrov, Ludmil B. 1; Nik-Zainal, Serena 1,2; Wedge, David C. 1; Aparicio, Samuel A. J. R. 3,4,5; Behjati, Sam 1,6; Biankin, Andrew V. 7,8,9,10,11; Bignell, Graham R. 1; Bolli, Niccolo 1,12,13; Borg, Ake 14; Borresen-Dale, Anne-Lise 15,16; Boyault, Sandrine 17; Burkhardt, Birgit 18,19; Butler, Adam P. 1; Caldas, Carlos 20; Davies, Helen R. 1; Desmedt, Christine 21; Eils, Roland 22; Eyfjord, Jorunn Erla 23; Foekens, John A. 24; Greaves, Mel 25; Hosoda, Fumie 26; Hutter, Barbara 22; Ilicic, Tomislav 1; Imbeaud, Sandrine 27,28; Imielinsk, Marcin 29; Jager, Natalie 22; Jones, David T. W. 30; Jones, David 1; Knappskog, Stian 31,32; Kool, Marcel 30; Lakhani, Sunil R. 33; Lopez-Otin, Carlos 34; Martin, Sancha 1; Munshi, Nikhil C. 35,36; Nakamura, Hiromi 26; Northcott, Paul A. 30; Pajic, Marina 7; Papaemmanuil, Elli 1; Paradiso, Angelo 37; Pearson, John V. 38; Puente, Xose S. 34; Raine, Keiran 1; Ramakrishna, Manasa 1; Richardson, Andrea L. 39,40,41; Richter, Julia 42; Rosenstiel, Philip 43; Schlesner, Matthias 22; Schumacher, Ton N. 44; Span, Paul N. 45; Teague, Jon W. 1; Totoki, Yasushi 26; Tutt, Andrew N. J. 46; Valdes-Mas, Rafael 34; van Buuren, Marit M. 44; van 't Veer, Laura 47; Vincent-Salomon, Anne 48; Waddell, Nicola 38; Yates, Lucy R. 1; Australian Pancreatic Cancer Genome Initiative *; ICGC Breast Cancer Consortium *; ICGC MMML-Seq Consortium *; ICGC PedBrain *; Zucman-Rossi, Jessica 27,28; Futreal, Andrew P. 1; McDermott, Ultan 1; Lichter, Peter 49; Meyerson, Matthew 29,39,40; Grimmond, Sean M. 38; Siebert, Reiner 42; Campo, Elias 50; Shibata, Tatsuhiro 26; Pfister, Stefan M. 30,51; Campbell, Peter J. 1,12,13; Stratton, Michael R. 1
[Article]
Nature.
500(7463):415-421, August 22, 2013.
(Format: HTML, PDF)
: 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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