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Signatures of mutational processes in human cancer

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, Åke LU and Borresen-Dale, Anne-Lise, et al. (2013) In Nature 500(7463). p.415-421
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... (More)
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. (Less)
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Nature
volume
500
issue
7463
pages
415 - 421
publisher
Nature Publishing Group
external identifiers
  • wos:000323316100026
  • scopus:84882837534
ISSN
0028-0836
DOI
10.1038/nature12477
language
English
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yes
id
2dcb9b2e-67f7-4ae6-9c7b-9a94442454b2 (old id 4025781)
date added to LUP
2013-10-01 15:11:29
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2019-10-16 01:15:27
@article{2dcb9b2e-67f7-4ae6-9c7b-9a94442454b2,
  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.},
  author       = {Alexandrov, Ludmil B. and Nik-Zainal, Serena and Wedge, David C. and Aparicio, Samuel A. J. R. and Behjati, Sam and Biankin, Andrew V. and Bignell, Graham R. and Bolli, Niccolo and Borg, Åke and Borresen-Dale, Anne-Lise and Boyault, Sandrine and Burkhardt, Birgit and Butler, Adam P. and Caldas, Carlos and Davies, Helen R. and Desmedt, Christine and Eils, Roland and Eyfjord, Jorunn Erla and Foekens, John A. and Greaves, Mel and Hosoda, Fumie and Hutter, Barbara and Ilicic, Tomislav and Imbeaud, Sandrine and Imielinsk, Marcin and Jaeger, Natalie and Jones, David T. W. and Jones, David and Knappskog, Stian and Kool, Marcel and Lakhani, Sunil R. and Lopez-Otin, Carlos and Martin, Sancha and Munshi, Nikhil C. and Nakamura, Hiromi and Northcott, Paul A. and Pajic, Marina and Papaemmanuil, Elli and Paradiso, Angelo and Pearson, John V. and Puente, Xose S. and Raine, Keiran and Ramakrishna, Manasa and Richardson, Andrea L. and Richter, Julia and Rosenstiel, Philip and Schlesner, Matthias and Schumacher, Ton N. and Span, Paul N. and Teague, Jon W. and Totoki, Yasushi and Tutt, Andrew N. J. and Valdes-Mas, Rafael and van Buuren, Marit M. and van 't Veer, Laura and Vincent-Salomon, Anne and Waddell, Nicola and Yates, Lucy R. and Zucman-Rossi, Jessica and Futreal, P. Andrew and McDermott, Ultan and Lichter, Peter and Meyerson, Matthew and Grimmond, Sean M. and Siebert, Reiner and Campo, Elias and Shibata, Tatsuhiro and Pfister, Stefan M. and Campbell, Peter J. and Stratton, Michael R.},
  issn         = {0028-0836},
  language     = {eng},
  number       = {7463},
  pages        = {415--421},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {Signatures of mutational processes in human cancer},
  url          = {http://dx.doi.org/10.1038/nature12477},
  volume       = {500},
  year         = {2013},
}