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Signatures of mutational processes in human cancer
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 mutati...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776390/ https://www.ncbi.nlm.nih.gov/pubmed/23945592 http://dx.doi.org/10.1038/nature12477 |
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author | 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 Børresen-Dale, Anne-Lise Boyault, Sandrine Burkhardt, Birgit Butler, Adam P. Caldas, Carlos Davies, Helen R. Desmedt, Christine Eils, Roland Eyfjörd, Jórunn Erla Foekens, John A. Greaves, Mel Hosoda, Fumie Hutter, Barbara Ilicic, Tomislav Imbeaud, Sandrine Imielinsk, Marcin Jäger, Natalie Jones, David T.W. Jones, David Knappskog, Stian Kool, Marcel Lakhani, Sunil R. López-Otín, 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. Valdés-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, Elías Shibata, Tatsuhiro Pfister, Stefan M. Campbell, Peter J. Stratton, Michael R. |
author_facet | 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 Børresen-Dale, Anne-Lise Boyault, Sandrine Burkhardt, Birgit Butler, Adam P. Caldas, Carlos Davies, Helen R. Desmedt, Christine Eils, Roland Eyfjörd, Jórunn Erla Foekens, John A. Greaves, Mel Hosoda, Fumie Hutter, Barbara Ilicic, Tomislav Imbeaud, Sandrine Imielinsk, Marcin Jäger, Natalie Jones, David T.W. Jones, David Knappskog, Stian Kool, Marcel Lakhani, Sunil R. López-Otín, 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. Valdés-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, Elías Shibata, Tatsuhiro Pfister, Stefan M. Campbell, Peter J. Stratton, Michael R. |
author_sort | Alexandrov, Ludmil B. |
collection | PubMed |
description | 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 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 etiology, prevention and therapy. |
format | Online Article Text |
id | pubmed-3776390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-37763902014-02-22 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, Ake Børresen-Dale, Anne-Lise Boyault, Sandrine Burkhardt, Birgit Butler, Adam P. Caldas, Carlos Davies, Helen R. Desmedt, Christine Eils, Roland Eyfjörd, Jórunn Erla Foekens, John A. Greaves, Mel Hosoda, Fumie Hutter, Barbara Ilicic, Tomislav Imbeaud, Sandrine Imielinsk, Marcin Jäger, Natalie Jones, David T.W. Jones, David Knappskog, Stian Kool, Marcel Lakhani, Sunil R. López-Otín, 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. Valdés-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, Elías Shibata, Tatsuhiro Pfister, Stefan M. Campbell, Peter J. Stratton, Michael R. Nature Article 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 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 etiology, prevention and therapy. 2013-08-14 2013-08-22 /pmc/articles/PMC3776390/ /pubmed/23945592 http://dx.doi.org/10.1038/nature12477 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article 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 Børresen-Dale, Anne-Lise Boyault, Sandrine Burkhardt, Birgit Butler, Adam P. Caldas, Carlos Davies, Helen R. Desmedt, Christine Eils, Roland Eyfjörd, Jórunn Erla Foekens, John A. Greaves, Mel Hosoda, Fumie Hutter, Barbara Ilicic, Tomislav Imbeaud, Sandrine Imielinsk, Marcin Jäger, Natalie Jones, David T.W. Jones, David Knappskog, Stian Kool, Marcel Lakhani, Sunil R. López-Otín, 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. Valdés-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, Elías Shibata, Tatsuhiro Pfister, Stefan M. Campbell, Peter J. Stratton, Michael R. Signatures of mutational processes in human cancer |
title | Signatures of mutational processes in human cancer |
title_full | Signatures of mutational processes in human cancer |
title_fullStr | Signatures of mutational processes in human cancer |
title_full_unstemmed | Signatures of mutational processes in human cancer |
title_short | Signatures of mutational processes in human cancer |
title_sort | signatures of mutational processes in human cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776390/ https://www.ncbi.nlm.nih.gov/pubmed/23945592 http://dx.doi.org/10.1038/nature12477 |
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