Signatures of mutational processes in human cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-08

AUTHORS

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 Greaves, Fumie Hosoda, Barbara Hutter, Tomislav Ilicic, Sandrine Imbeaud, Marcin Imielinski, Natalie Jäger, David T. W. Jones, David Jones, Stian Knappskog, Marcel Kool, 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, Australian Pancreatic Cancer Genome Initiative, ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, ICGC PedBrain, 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

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. More... »

PAGES

415

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  • Journal

    TITLE

    Nature

    ISSUE

    7463

    VOLUME

    500

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature12477

    DOI

    http://dx.doi.org/10.1038/nature12477

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050004918

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23945592


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