Signatures of mutational processes in human cancer.

Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Aparicio, Sajr, Behjati, S., Biankin, A. V., Bignell, G. R., Bolli, N., Borg, A., Borresen-Dale, A. L., Boyault, S., Burkhardt, B., Butler, A. P., Caldas, C., Davies, H. R., Desmedt, C., Eils, R., Eyfjord, J. E., Foekens, J. A., Greaves, M., Hosoda, F., Hutter, B., Ilicic, T., Imbeaud, S., Imielinsk, M., Jager, N., Jones, D. T. W., Jones, D., Knappskog, S., Kool, M., Lakhani, S. R., Lopez-Otin, C., Martin, S., Munshi, N. C., Nakamura, H., Northcott, P. A., Pajic, M., Papaemmanuil, E., Paradiso, A., Pearson, J. V., Puente, X. S., Raine, K., Ramakrishna, M., Richardson, A. L., Richter, J., Rosenstiel, Philip, Schlesner, M., Schumacher, T. N., Span, P. N., Teague, J. W., Totoki, Y., Tutt, A. N. J., Valdes-Mas, R., van Buuren, M. M., van 't Veer, L., Vincent-Salomon, A., Waddell, N., Yates, L. R., Zucman-Rossi, J., Futreal, P. A., McDermott, U., Lichter, P., Meyerson, M., Grimmond, S. M., Siebert, R., Campo, E., Shibata, T., Pfister, S. M., Campbell, P. J., Stratton, M. R., Australian Pancreatic Canc, Genome, Consortium, Icgc Breast Canc, Consortium, Icgc Mmml- Seq and PedBrain, Icgc (2013) Signatures of mutational processes in human cancer. Nature, 500 (7463). 415-+. DOI 10.1038/nature12477.

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Supplementary data:


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.

Document Type: Article
Additional Information: Times Cited: 66 Alexandrov, Ludmil B. Nik-Zainal, Serena Wedge, David C. Aparicio, Samuel A. J. R. Behjati, Sam Biankin, Andrew V. Bignell, Graham R. Bolli, Niccolo Borg, Ake Borresen-Dale, Anne-Lise Boyault, Sandrine Burkhardt, Birgit Butler, Adam P. Caldas, Carlos Davies, Helen R. Desmedt, Christine Eils, Roland Eyfjord, Jorunn Erla Foekens, John A. Greaves, Mel Hosoda, Fumie Hutter, Barbara Ilicic, Tomislav Imbeaud, Sandrine Imielinsk, Marcin Jaeger, Natalie Jones, David T. W. Jones, David Knappskog, Stian Kool, Marcel Lakhani, Sunil R. Lopez-Otin, Carlos Martin, Sancha Munshi, Nikhil C. Nakamura, Hiromi Northcott, Paul A. Pajic, Marina Papaemmanuil, Elli Paradiso, Angelo Pearson, John V. Puente, Xose S. Raine, Keiran Ramakrishna, Manasa Richardson, Andrea L. Richter, Julia Rosenstiel, Philip Schlesner, Matthias Schumacher, Ton N. Span, Paul N. Teague, Jon W. Totoki, Yasushi Tutt, Andrew N. J. Valdes-Mas, Rafael van Buuren, Marit M. van 't Veer, Laura Vincent-Salomon, Anne Waddell, Nicola Yates, Lucy R. Zucman-Rossi, Jessica Futreal, P. Andrew McDermott, Ultan Lichter, Peter Meyerson, Matthew Grimmond, Sean M. Siebert, Reiner Campo, Elias Shibata, Tatsuhiro Pfister, Stefan M. Campbell, Peter J. Stratton, Michael R.
Keywords: Cancer
Research affiliation: Kiel University
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
Open Access Journal?: No
DOI etc.: 10.1038/nature12477
ISSN: 0028-0836
Projects: Future Ocean
Date Deposited: 08 Jul 2014 08:48
Last Modified: 23 Sep 2019 21:53

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