Signatures of mutational processes in human cancer

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, 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 and Michael R. Stratton ()
Additional contact information
Ludmil B. Alexandrov: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Serena Nik-Zainal: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
David C. Wedge: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Samuel A. J. R. Aparicio: Molecular Oncology, Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada.
Sam Behjati: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Andrew V. Biankin: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Graham R. Bignell: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Niccolò Bolli: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Ake Borg: Lund University, SE-221 85 Lund, Sweden.
Anne-Lise Børresen-Dale: Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
Sandrine Boyault: Plateforme de Bioinformatique Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon Cedex 08, France.
Birgit Burkhardt: University Children’s Hospital, 48149 Münster, Germany.
Adam P. Butler: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Carlos Caldas: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Helen R. Davies: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Christine Desmedt: Breast Cancer Translational Res Lab -BCTL, Université Libre de Bruxelles—Institut Jules Bordet, Boulevard de Waterloo, 125, B-1000 Brussels, Belgium.
Roland Eils: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Jórunn Erla Eyfjörd: Cancer Research Laboratory, Faculty of Medicine, Biomedical Centre, University of Iceland, 101 Reykjavik, Iceland.
John A. Foekens: Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands.
Mel Greaves: Institute of Cancer Research, London SM2 5NG, UK.
Fumie Hosoda: National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Barbara Hutter: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Tomislav Ilicic: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Sandrine Imbeaud: INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), 75475 Paris, France.
Marcin Imielinski: The Broad Institute of MIT and Harvard
Natalie Jäger: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
David T. W. Jones: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
David Jones: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Stian Knappskog: Section of Oncology, University of Bergen, 5020 Bergen, Norway.
Marcel Kool: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Sunil R. Lakhani: The University of Queensland Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston 4029, Brisbane, Queensland, Australia.
Carlos López-Otín: IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain.
Sancha Martin: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Nikhil C. Munshi: Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School
Hiromi Nakamura: National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Paul A. Northcott: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Marina Pajic: Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Elli Papaemmanuil: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Angelo Paradiso: Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126 Bari, Italy.
John V. Pearson: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Xose S. Puente: IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain.
Keiran Raine: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Manasa Ramakrishna: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Andrea L. Richardson: Dana-Farber Cancer Institute, 450 Brookline Avenue
Julia Richter: Institute of Human Genetics, Christian-Albrechts-University, 24118 Kiel, Germany.
Philip Rosenstiel: Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24118 Kiel, Germany.
Matthias Schlesner: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Ton N. Schumacher: The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Paul N. Span: Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen, The Netherlands.
Jon W. Teague: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Yasushi Totoki: National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Andrew N. J. Tutt: Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, London SW3 6JB, UK.
Rafael Valdés-Mas: IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain.
Marit M. van Buuren: The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Laura van ’t Veer: The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands.
Anne Vincent-Salomon: Institut Curie, Departement de Pathologie, INSERM U830, 26 rue d’Ulm, 75248 Paris Cedex 05, France.
Nicola Waddell: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Lucy R. Yates: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Jessica Zucman-Rossi: INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), 75475 Paris, France.
P. Andrew Futreal: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Ultan McDermott: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Peter Lichter: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Matthew Meyerson: The Broad Institute of MIT and Harvard
Sean M. Grimmond: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
Reiner Siebert: Institute of Human Genetics, Christian-Albrechts-University, 24118 Kiel, Germany.
Elías Campo: Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Universitat de Barcelona, IDIBAPS, 08036 Barcelona, Spain.
Tatsuhiro Shibata: National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Stefan M. Pfister: German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Peter J. Campbell: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Michael R. Stratton: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.

Nature, 2013, vol. 500, issue 7463, 415-421

Abstract: 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.

Date: 2013
References: Add references at CitEc
Citations: View citations in EconPapers (67)

Downloads: (external link)
https://www.nature.com/articles/nature12477 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:500:y:2013:i:7463:d:10.1038_nature12477

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature12477

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().