Serveur d'exploration sur les relations entre la France et l'Australie

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Signatures of mutational processes in human cancer

Identifieur interne : 001880 ( Pmc/Checkpoint ); précédent : 001879; suivant : 001881

Signatures of mutational processes in human cancer

Auteurs : Ludmil B. Alexandrov ; Serena Nik-Zainal ; David C. Wedge ; Samuel A. J. R. Aparicio [Canada] ; Sam Behjati [Royaume-Uni] ; Andrew V. Biankin [Royaume-Uni, Australie] ; Graham R. Bignell ; Niccolo Bolli [Royaume-Uni] ; Ake Borg [Suède] ; Anne-Lise B Rresen-Dale [Norvège] ; Sandrine Boyault ; Birgit Burkhardt [Allemagne] ; Adam P. Butler ; Carlos Caldas [Royaume-Uni] ; Helen R. Davies ; Christine Desmedt [Belgique] ; Roland Eils [Allemagne] ; J Runn Erla Eyfjörd [Islande] ; John A. Foekens [Pays-Bas] ; Mel Greaves [Royaume-Uni] ; Fumie Hosoda [Japon] ; Barbara Hutter [Allemagne] ; Tomislav Ilicic ; Sandrine Imbeaud [France] ; Marcin Imielinsk [États-Unis] ; Natalie J Ger [Allemagne] ; David T. W. Jones [Allemagne] ; David Jones ; Stian Knappskog [Norvège] ; Marcel Kool [Allemagne] ; Sunil R. Lakhani [Australie] ; Carlos L Pez-Otín [Espagne] ; Sancha Martin ; Nikhil C. Munshi [États-Unis] ; Hiromi Nakamura [Japon] ; Paul A. Northcott [Allemagne] ; Marina Pajic [Royaume-Uni] ; Elli Papaemmanuil ; Angelo Paradiso [Italie] ; John V. Pearson [Australie] ; Xose S. Puente [Espagne] ; Keiran Raine ; Manasa Ramakrishna ; Andrea L. Richardson [États-Unis] ; Julia Richter [Allemagne] ; Philip Rosenstiel [Allemagne] ; Matthias Schlesner [Allemagne] ; Ton N. Schumacher [Pays-Bas] ; Paul N. Span [Pays-Bas] ; Jon W. Teague ; Yasushi Totoki [Japon] ; Andrew N. J. Tutt [Royaume-Uni] ; Rafael Valdés-Mas [Espagne] ; Marit M. Van Buuren [Pays-Bas] ; Laura Van Veer [Pays-Bas] ; Anne Vincent-Salomon [France] ; Nicola Waddell [Australie] ; Lucy R. Yates ; Jessica Zucman-Rossi [France] ; P. Andrew Futreal ; Ultan Mcdermott ; Peter Lichter [Allemagne] ; Matthew Meyerson [États-Unis] ; Sean M. Grimmond [Australie] ; Reiner Siebert [Allemagne] ; Elías Campo [Espagne] ; Tatsuhiro Shibata [Japon] ; Stefan M. Pfister [Allemagne] ; Peter J. Campbell [Royaume-Uni] ; Michael R. Stratton

Source :

RBID : PMC:3776390

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 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.


Url:
DOI: 10.1038/nature12477
PubMed: 23945592
PubMed Central: 3776390


Affiliations:


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PMC:3776390

Le document en format XML

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<name sortKey="B Rresen Dale, Anne Lise" sort="B Rresen Dale, Anne Lise" uniqKey="B Rresen Dale A" first="Anne-Lise" last="B Rresen-Dale">Anne-Lise B Rresen-Dale</name>
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<name sortKey="Boyault, Sandrine" sort="Boyault, Sandrine" uniqKey="Boyault S" first="Sandrine" last="Boyault">Sandrine Boyault</name>
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<name sortKey="Caldas, Carlos" sort="Caldas, Carlos" uniqKey="Caldas C" first="Carlos" last="Caldas">Carlos Caldas</name>
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<name sortKey="Davies, Helen R" sort="Davies, Helen R" uniqKey="Davies H" first="Helen R." last="Davies">Helen R. Davies</name>
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<name sortKey="Desmedt, Christine" sort="Desmedt, Christine" uniqKey="Desmedt C" first="Christine" last="Desmedt">Christine Desmedt</name>
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<name sortKey="Eyfjord, J Runn Erla" sort="Eyfjord, J Runn Erla" uniqKey="Eyfjord J" first="J Runn Erla" last="Eyfjörd">J Runn Erla Eyfjörd</name>
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<name sortKey="Foekens, John A" sort="Foekens, John A" uniqKey="Foekens J" first="John A." last="Foekens">John A. Foekens</name>
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<nlm:aff id="A24">Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands</nlm:aff>
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<name sortKey="Hosoda, Fumie" sort="Hosoda, Fumie" uniqKey="Hosoda F" first="Fumie" last="Hosoda">Fumie Hosoda</name>
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<name sortKey="Hutter, Barbara" sort="Hutter, Barbara" uniqKey="Hutter B" first="Barbara" last="Hutter">Barbara Hutter</name>
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<name sortKey="Ilicic, Tomislav" sort="Ilicic, Tomislav" uniqKey="Ilicic T" first="Tomislav" last="Ilicic">Tomislav Ilicic</name>
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<name sortKey="Imbeaud, Sandrine" sort="Imbeaud, Sandrine" uniqKey="Imbeaud S" first="Sandrine" last="Imbeaud">Sandrine Imbeaud</name>
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<nlm:aff id="A28">INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris, France</nlm:aff>
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<nlm:aff id="A29">Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France</nlm:aff>
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<orgName type="university">Université Paris-Descartes</orgName>
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<name sortKey="Imielinsk, Marcin" sort="Imielinsk, Marcin" uniqKey="Imielinsk M" first="Marcin" last="Imielinsk">Marcin Imielinsk</name>
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<nlm:aff id="A30">The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA</nlm:aff>
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<region type="state">Massachusetts</region>
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<name sortKey="J Ger, Natalie" sort="J Ger, Natalie" uniqKey="J Ger N" first="Natalie" last="J Ger">Natalie J Ger</name>
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<nlm:aff id="A22">Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</nlm:aff>
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<wicri:regionArea>Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg</wicri:regionArea>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jones, David T W" sort="Jones, David T W" uniqKey="Jones D" first="David T. W." last="Jones">David T. W. Jones</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jones, David" sort="Jones, David" uniqKey="Jones D" first="David" last="Jones">David Jones</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Knappskog, Stian" sort="Knappskog, Stian" uniqKey="Knappskog S" first="Stian" last="Knappskog">Stian Knappskog</name>
<affiliation wicri:level="1">
<nlm:aff id="A31">Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen</wicri:regionArea>
<wicri:noRegion>5020 Bergen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A32">Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Oncology, Haukeland University Hospital, 5021 Bergen</wicri:regionArea>
<wicri:noRegion>5021 Bergen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kool, Marcel" sort="Kool, Marcel" uniqKey="Kool M" first="Marcel" last="Kool">Marcel Kool</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lakhani, Sunil R" sort="Lakhani, Sunil R" uniqKey="Lakhani S" first="Sunil R." last="Lakhani">Sunil R. Lakhani</name>
<affiliation wicri:level="1">
<nlm:aff id="A33">The University of Queensland Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston 4029,Brisbane, QLD, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Queensland Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston 4029,Brisbane, QLD</wicri:regionArea>
<wicri:noRegion>QLD</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="L Pez Otin, Carlos" sort="L Pez Otin, Carlos" uniqKey="L Pez Otin C" first="Carlos" last="L Pez-Otín">Carlos L Pez-Otín</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo</wicri:regionArea>
<wicri:noRegion>33006 Oviedo</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Martin, Sancha" sort="Martin, Sancha" uniqKey="Martin S" first="Sancha" last="Martin">Sancha Martin</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Munshi, Nikhil C" sort="Munshi, Nikhil C" uniqKey="Munshi N" first="Nikhil C." last="Munshi">Nikhil C. Munshi</name>
<affiliation wicri:level="2">
<nlm:aff id="A35">Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A36">Boston Veterans Administration Healthcare System, West Roxbury, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Boston Veterans Administration Healthcare System, West Roxbury</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Nakamura, Hiromi" sort="Nakamura, Hiromi" uniqKey="Nakamura H" first="Hiromi" last="Nakamura">Hiromi Nakamura</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045</wicri:regionArea>
<wicri:noRegion>104-0045</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Northcott, Paul A" sort="Northcott, Paul A" uniqKey="Northcott P" first="Paul A." last="Northcott">Paul A. Northcott</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pajic, Marina" sort="Pajic, Marina" uniqKey="Pajic M" first="Marina" last="Pajic">Marina Pajic</name>
<affiliation wicri:level="4">
<nlm:aff id="A7">Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName>
<settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Papaemmanuil, Elli" sort="Papaemmanuil, Elli" uniqKey="Papaemmanuil E" first="Elli" last="Papaemmanuil">Elli Papaemmanuil</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Paradiso, Angelo" sort="Paradiso, Angelo" uniqKey="Paradiso A" first="Angelo" last="Paradiso">Angelo Paradiso</name>
<affiliation wicri:level="1">
<nlm:aff id="A37">Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126, Bari, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126, Bari</wicri:regionArea>
<wicri:noRegion>Bari</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Pearson, John V" sort="Pearson, John V" uniqKey="Pearson J" first="John V." last="Pearson">John V. Pearson</name>
<affiliation wicri:level="1">
<nlm:aff id="A38">Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072</wicri:regionArea>
<wicri:noRegion>Queensland 4072</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Puente, Xose S" sort="Puente, Xose S" uniqKey="Puente X" first="Xose S." last="Puente">Xose S. Puente</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo</wicri:regionArea>
<wicri:noRegion>33006 Oviedo</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Ramakrishna, Manasa" sort="Ramakrishna, Manasa" uniqKey="Ramakrishna M" first="Manasa" last="Ramakrishna">Manasa Ramakrishna</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Richardson, Andrea L" sort="Richardson, Andrea L" uniqKey="Richardson A" first="Andrea L." last="Richardson">Andrea L. Richardson</name>
<affiliation wicri:level="2">
<nlm:aff id="A39">Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A40">Harvard Medical School, Boston, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Harvard Medical School, Boston, Massachusetts</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A41">Department of Pathology, Brigham and Women’s Hospital 75 Francis St. Boston, MA 02115, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, Brigham and Women’s Hospital 75 Francis St. Boston, MA 02115</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Richter, Julia" sort="Richter, Julia" uniqKey="Richter J" first="Julia" last="Richter">Julia Richter</name>
<affiliation wicri:level="3">
<nlm:aff id="A42">Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, Christian-Albrechts-University, Kiel</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Schleswig-Holstein</region>
<settlement type="city">Kiel</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Rosenstiel, Philip" sort="Rosenstiel, Philip" uniqKey="Rosenstiel P" first="Philip" last="Rosenstiel">Philip Rosenstiel</name>
<affiliation wicri:level="3">
<nlm:aff id="A43">Institute of Clinical Molecular Biology, Christian-Albrechts-University,Kiel, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Clinical Molecular Biology, Christian-Albrechts-University,Kiel</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Schleswig-Holstein</region>
<settlement type="city">Kiel</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schlesner, Matthias" sort="Schlesner, Matthias" uniqKey="Schlesner M" first="Matthias" last="Schlesner">Matthias Schlesner</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schumacher, Ton N" sort="Schumacher, Ton N" uniqKey="Schumacher T" first="Ton N." last="Schumacher">Ton N. Schumacher</name>
<affiliation wicri:level="3">
<nlm:aff id="A44">Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Span, Paul N" sort="Span, Paul N" uniqKey="Span P" first="Paul N." last="Span">Paul N. Span</name>
<affiliation wicri:level="1">
<nlm:aff id="A45">Department of Radiation Oncology and department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen,the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Radiation Oncology and department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Teague, Jon W" sort="Teague, Jon W" uniqKey="Teague J" first="Jon W." last="Teague">Jon W. Teague</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Totoki, Yasushi" sort="Totoki, Yasushi" uniqKey="Totoki Y" first="Yasushi" last="Totoki">Yasushi Totoki</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045</wicri:regionArea>
<wicri:noRegion>104-0045</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tutt, Andrew N J" sort="Tutt, Andrew N J" uniqKey="Tutt A" first="Andrew N. J." last="Tutt">Andrew N. J. Tutt</name>
<affiliation wicri:level="3">
<nlm:aff id="A46">Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Valdes Mas, Rafael" sort="Valdes Mas, Rafael" uniqKey="Valdes Mas R" first="Rafael" last="Valdés-Mas">Rafael Valdés-Mas</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo</wicri:regionArea>
<wicri:noRegion>33006 Oviedo</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Van Buuren, Marit M" sort="Van Buuren, Marit M" uniqKey="Van Buuren M" first="Marit M." last="Van Buuren">Marit M. Van Buuren</name>
<affiliation wicri:level="3">
<nlm:aff id="A44">Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Van Veer, Laura" sort="Van Veer, Laura" uniqKey="Van Veer L" first="Laura" last="Van Veer">Laura Van Veer</name>
<affiliation wicri:level="1">
<nlm:aff id="A47">The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam</wicri:regionArea>
<wicri:noRegion>1066 CX Amsterdam</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vincent Salomon, Anne" sort="Vincent Salomon, Anne" uniqKey="Vincent Salomon A" first="Anne" last="Vincent-Salomon">Anne Vincent-Salomon</name>
<affiliation wicri:level="1">
<nlm:aff id="A48">Institut Curie , Departement de Pathologie, INSERM U830, 26 rue d’Ulm 75248 PARIS CEDEX 05, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Curie , Departement de Pathologie, INSERM U830, 26 rue d’Ulm 75248 PARIS CEDEX 05</wicri:regionArea>
<wicri:noRegion>75248 PARIS CEDEX 05</wicri:noRegion>
<wicri:noRegion>75248 PARIS CEDEX 05</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Waddell, Nicola" sort="Waddell, Nicola" uniqKey="Waddell N" first="Nicola" last="Waddell">Nicola Waddell</name>
<affiliation wicri:level="1">
<nlm:aff id="A38">Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072</wicri:regionArea>
<wicri:noRegion>Queensland 4072</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yates, Lucy R" sort="Yates, Lucy R" uniqKey="Yates L" first="Lucy R." last="Yates">Lucy R. Yates</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Zucman Rossi, Jessica" sort="Zucman Rossi, Jessica" uniqKey="Zucman Rossi J" first="Jessica" last="Zucman-Rossi">Jessica Zucman-Rossi</name>
<affiliation wicri:level="3">
<nlm:aff id="A28">INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A29">Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris-Descartes</orgName>
</affiliation>
</author>
<author>
<name sortKey="Futreal, P Andrew" sort="Futreal, P Andrew" uniqKey="Futreal P" first="P. Andrew" last="Futreal">P. Andrew Futreal</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Mcdermott, Ultan" sort="Mcdermott, Ultan" uniqKey="Mcdermott U" first="Ultan" last="Mcdermott">Ultan Mcdermott</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Lichter, Peter" sort="Lichter, Peter" uniqKey="Lichter P" first="Peter" last="Lichter">Peter Lichter</name>
<affiliation wicri:level="3">
<nlm:aff id="A49">Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Meyerson, Matthew" sort="Meyerson, Matthew" uniqKey="Meyerson M" first="Matthew" last="Meyerson">Matthew Meyerson</name>
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<nlm:aff id="A42">Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany</nlm:aff>
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<name sortKey="Pfister, Stefan M" sort="Pfister, Stefan M" uniqKey="Pfister S" first="Stefan M." last="Pfister">Stefan M. Pfister</name>
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<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
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<affiliation>
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<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
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<affiliation wicri:level="1">
<nlm:aff id="A12">Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK</nlm:aff>
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<wicri:regionArea>Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ</wicri:regionArea>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
<affiliation>
<nlm:aff id="A2">Department of Medical Genetics, Box 134, Addenbrooke’s Hospital NHS Trust, Hills Road, Cambridge CB2 0QQ</nlm:aff>
<wicri:noCountry code="subfield">Cambridge CB2 0QQ</wicri:noCountry>
</affiliation>
</author>
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<name sortKey="Wedge, David C" sort="Wedge, David C" uniqKey="Wedge D" first="David C." last="Wedge">David C. Wedge</name>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
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<name sortKey="Aparicio, Samuel A J R" sort="Aparicio, Samuel A J R" uniqKey="Aparicio S" first="Samuel A. J. R." last="Aparicio">Samuel A. J. R. Aparicio</name>
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<nlm:aff id="A3">Molecular Oncology, Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
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<nlm:aff id="A4">Centre for Translational and Applied Genomics, Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Centre for Translational and Applied Genomics, Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A5">Department of Pathology, University of British Columbia, G227-2211 Wesbrook Mall, British Columbia, Vancouver V6T 2B5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pathology, University of British Columbia, G227-2211 Wesbrook Mall, British Columbia, Vancouver V6T 2B5</wicri:regionArea>
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<name sortKey="Behjati, Sam" sort="Behjati, Sam" uniqKey="Behjati S" first="Sam" last="Behjati">Sam Behjati</name>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A6">Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
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<placeName>
<settlement type="city">Cambridge</settlement>
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<name sortKey="Biankin, Andrew V" sort="Biankin, Andrew V" uniqKey="Biankin A" first="Andrew V." last="Biankin">Andrew V. Biankin</name>
<affiliation wicri:level="4">
<nlm:aff id="A7">Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD</wicri:regionArea>
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<settlement type="city">Glasgow</settlement>
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<affiliation wicri:level="1">
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland G4 0SF</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A9">The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A10">Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="A11">South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170</wicri:regionArea>
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<name sortKey="Bignell, Graham R" sort="Bignell, Graham R" uniqKey="Bignell G" first="Graham R." last="Bignell">Graham R. Bignell</name>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Bolli, Niccolo" sort="Bolli, Niccolo" uniqKey="Bolli N" first="Niccolo" last="Bolli">Niccolo Bolli</name>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ</wicri:regionArea>
<wicri:noRegion>Cambridge CB2 0QQ</wicri:noRegion>
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<affiliation wicri:level="4">
<nlm:aff id="A13">Department of Haematology, University of Cambridge, Cambridge CB2 2XY, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge CB2 2XY</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
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<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
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</affiliation>
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<name sortKey="Borg, Ake" sort="Borg, Ake" uniqKey="Borg A" first="Ake" last="Borg">Ake Borg</name>
<affiliation wicri:level="1">
<nlm:aff id="A14">Department of Oncology, Lund University, SE-221 85 Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Oncology, Lund University, SE-221 85 Lund</wicri:regionArea>
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</author>
<author>
<name sortKey="B Rresen Dale, Anne Lise" sort="B Rresen Dale, Anne Lise" uniqKey="B Rresen Dale A" first="Anne-Lise" last="B Rresen-Dale">Anne-Lise B Rresen-Dale</name>
<affiliation wicri:level="1">
<nlm:aff id="A15">Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, 0310 Oslo</wicri:regionArea>
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<settlement type="city">Oslo</settlement>
<region nuts="2">Østlandet</region>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A16">The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo</wicri:regionArea>
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</author>
<author>
<name sortKey="Boyault, Sandrine" sort="Boyault, Sandrine" uniqKey="Boyault S" first="Sandrine" last="Boyault">Sandrine Boyault</name>
<affiliation>
<nlm:aff id="A17">Plateforme de Bioinformatique Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laennec, 69373 LYON CEDEX 08</nlm:aff>
<wicri:noCountry code="subfield">69373 LYON CEDEX 08</wicri:noCountry>
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</author>
<author>
<name sortKey="Burkhardt, Birgit" sort="Burkhardt, Birgit" uniqKey="Burkhardt B" first="Birgit" last="Burkhardt">Birgit Burkhardt</name>
<affiliation wicri:level="3">
<nlm:aff id="A18">NHL-BFM Study Center and Department of Pediatric Hematology and Oncology, University Children’s Hospital, Münster, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A19">NHL-BFM Study Center and Department of Pediatric Hematology and Oncology, University Children’s Hospital, Giessen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>NHL-BFM Study Center and Department of Pediatric Hematology and Oncology, University Children’s Hospital, Giessen</wicri:regionArea>
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<wicri:noRegion>Giessen</wicri:noRegion>
<wicri:noRegion>Giessen</wicri:noRegion>
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</author>
<author>
<name sortKey="Butler, Adam P" sort="Butler, Adam P" uniqKey="Butler A" first="Adam P." last="Butler">Adam P. Butler</name>
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<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Caldas, Carlos" sort="Caldas, Carlos" uniqKey="Caldas C" first="Carlos" last="Caldas">Carlos Caldas</name>
<affiliation wicri:level="4">
<nlm:aff id="A20">Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
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</affiliation>
</author>
<author>
<name sortKey="Davies, Helen R" sort="Davies, Helen R" uniqKey="Davies H" first="Helen R." last="Davies">Helen R. Davies</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Desmedt, Christine" sort="Desmedt, Christine" uniqKey="Desmedt C" first="Christine" last="Desmedt">Christine Desmedt</name>
<affiliation wicri:level="1">
<nlm:aff id="A21">Breast Cancer Translational Res Lab - BCTL, Université Libre de Bruxelles - Institut Jules Bordet, Boulevard de Waterloo, 125, B-1000 Brussels</nlm:aff>
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<wicri:regionArea>Breast Cancer Translational Res Lab - BCTL, Université Libre de Bruxelles - Institut Jules Bordet, Boulevard de Waterloo, 125, B-1000 Brussels</wicri:regionArea>
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</author>
<author>
<name sortKey="Eils, Roland" sort="Eils, Roland" uniqKey="Eils R" first="Roland" last="Eils">Roland Eils</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg</wicri:regionArea>
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<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
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</affiliation>
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<author>
<name sortKey="Eyfjord, J Runn Erla" sort="Eyfjord, J Runn Erla" uniqKey="Eyfjord J" first="J Runn Erla" last="Eyfjörd">J Runn Erla Eyfjörd</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Cancer Research Laboratory, Faculty of Medicine, Biomedical Centre, University of Iceland, 101 Reykjavik, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
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</author>
<author>
<name sortKey="Foekens, John A" sort="Foekens, John A" uniqKey="Foekens J" first="John A." last="Foekens">John A. Foekens</name>
<affiliation wicri:level="3">
<nlm:aff id="A24">Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam</wicri:regionArea>
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<settlement type="city">Rotterdam</settlement>
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</affiliation>
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<author>
<name sortKey="Greaves, Mel" sort="Greaves, Mel" uniqKey="Greaves M" first="Mel" last="Greaves">Mel Greaves</name>
<affiliation wicri:level="3">
<nlm:aff id="A25">Department of Haemato-oncology, Institute of Cancer Research, London</nlm:aff>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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<wicri:orgArea>Department of Haemato-oncology, Institute of Cancer Research</wicri:orgArea>
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</author>
<author>
<name sortKey="Hosoda, Fumie" sort="Hosoda, Fumie" uniqKey="Hosoda F" first="Fumie" last="Hosoda">Fumie Hosoda</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045</wicri:regionArea>
<wicri:noRegion>104-0045</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hutter, Barbara" sort="Hutter, Barbara" uniqKey="Hutter B" first="Barbara" last="Hutter">Barbara Hutter</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Ilicic, Tomislav" sort="Ilicic, Tomislav" uniqKey="Ilicic T" first="Tomislav" last="Ilicic">Tomislav Ilicic</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Imbeaud, Sandrine" sort="Imbeaud, Sandrine" uniqKey="Imbeaud S" first="Sandrine" last="Imbeaud">Sandrine Imbeaud</name>
<affiliation wicri:level="3">
<nlm:aff id="A28">INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A29">Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris-Descartes</orgName>
</affiliation>
</author>
<author>
<name sortKey="Imielinsk, Marcin" sort="Imielinsk, Marcin" uniqKey="Imielinsk M" first="Marcin" last="Imielinsk">Marcin Imielinsk</name>
<affiliation wicri:level="2">
<nlm:aff id="A30">The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Broad Institute of MIT and Harvard, Cambridge, Massachusetts</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="J Ger, Natalie" sort="J Ger, Natalie" uniqKey="J Ger N" first="Natalie" last="J Ger">Natalie J Ger</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jones, David T W" sort="Jones, David T W" uniqKey="Jones D" first="David T. W." last="Jones">David T. W. Jones</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jones, David" sort="Jones, David" uniqKey="Jones D" first="David" last="Jones">David Jones</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Knappskog, Stian" sort="Knappskog, Stian" uniqKey="Knappskog S" first="Stian" last="Knappskog">Stian Knappskog</name>
<affiliation wicri:level="1">
<nlm:aff id="A31">Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen</wicri:regionArea>
<wicri:noRegion>5020 Bergen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A32">Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Oncology, Haukeland University Hospital, 5021 Bergen</wicri:regionArea>
<wicri:noRegion>5021 Bergen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kool, Marcel" sort="Kool, Marcel" uniqKey="Kool M" first="Marcel" last="Kool">Marcel Kool</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lakhani, Sunil R" sort="Lakhani, Sunil R" uniqKey="Lakhani S" first="Sunil R." last="Lakhani">Sunil R. Lakhani</name>
<affiliation wicri:level="1">
<nlm:aff id="A33">The University of Queensland Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston 4029,Brisbane, QLD, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The University of Queensland Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston 4029,Brisbane, QLD</wicri:regionArea>
<wicri:noRegion>QLD</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="L Pez Otin, Carlos" sort="L Pez Otin, Carlos" uniqKey="L Pez Otin C" first="Carlos" last="L Pez-Otín">Carlos L Pez-Otín</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo</wicri:regionArea>
<wicri:noRegion>33006 Oviedo</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Martin, Sancha" sort="Martin, Sancha" uniqKey="Martin S" first="Sancha" last="Martin">Sancha Martin</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Munshi, Nikhil C" sort="Munshi, Nikhil C" uniqKey="Munshi N" first="Nikhil C." last="Munshi">Nikhil C. Munshi</name>
<affiliation wicri:level="2">
<nlm:aff id="A35">Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A36">Boston Veterans Administration Healthcare System, West Roxbury, MA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Boston Veterans Administration Healthcare System, West Roxbury</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Nakamura, Hiromi" sort="Nakamura, Hiromi" uniqKey="Nakamura H" first="Hiromi" last="Nakamura">Hiromi Nakamura</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045</wicri:regionArea>
<wicri:noRegion>104-0045</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Northcott, Paul A" sort="Northcott, Paul A" uniqKey="Northcott P" first="Paul A." last="Northcott">Paul A. Northcott</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pajic, Marina" sort="Pajic, Marina" uniqKey="Pajic M" first="Marina" last="Pajic">Marina Pajic</name>
<affiliation wicri:level="4">
<nlm:aff id="A7">Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD</wicri:regionArea>
<orgName type="university">Université de Glasgow</orgName>
<placeName>
<settlement type="city">Glasgow</settlement>
<region type="country">Écosse</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Papaemmanuil, Elli" sort="Papaemmanuil, Elli" uniqKey="Papaemmanuil E" first="Elli" last="Papaemmanuil">Elli Papaemmanuil</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Paradiso, Angelo" sort="Paradiso, Angelo" uniqKey="Paradiso A" first="Angelo" last="Paradiso">Angelo Paradiso</name>
<affiliation wicri:level="1">
<nlm:aff id="A37">Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126, Bari, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126, Bari</wicri:regionArea>
<wicri:noRegion>Bari</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Pearson, John V" sort="Pearson, John V" uniqKey="Pearson J" first="John V." last="Pearson">John V. Pearson</name>
<affiliation wicri:level="1">
<nlm:aff id="A38">Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072</wicri:regionArea>
<wicri:noRegion>Queensland 4072</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Puente, Xose S" sort="Puente, Xose S" uniqKey="Puente X" first="Xose S." last="Puente">Xose S. Puente</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo</wicri:regionArea>
<wicri:noRegion>33006 Oviedo</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Ramakrishna, Manasa" sort="Ramakrishna, Manasa" uniqKey="Ramakrishna M" first="Manasa" last="Ramakrishna">Manasa Ramakrishna</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Richardson, Andrea L" sort="Richardson, Andrea L" uniqKey="Richardson A" first="Andrea L." last="Richardson">Andrea L. Richardson</name>
<affiliation wicri:level="2">
<nlm:aff id="A39">Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A40">Harvard Medical School, Boston, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Harvard Medical School, Boston, Massachusetts</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A41">Department of Pathology, Brigham and Women’s Hospital 75 Francis St. Boston, MA 02115, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, Brigham and Women’s Hospital 75 Francis St. Boston, MA 02115</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Richter, Julia" sort="Richter, Julia" uniqKey="Richter J" first="Julia" last="Richter">Julia Richter</name>
<affiliation wicri:level="3">
<nlm:aff id="A42">Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, Christian-Albrechts-University, Kiel</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Schleswig-Holstein</region>
<settlement type="city">Kiel</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Rosenstiel, Philip" sort="Rosenstiel, Philip" uniqKey="Rosenstiel P" first="Philip" last="Rosenstiel">Philip Rosenstiel</name>
<affiliation wicri:level="3">
<nlm:aff id="A43">Institute of Clinical Molecular Biology, Christian-Albrechts-University,Kiel, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Clinical Molecular Biology, Christian-Albrechts-University,Kiel</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Schleswig-Holstein</region>
<settlement type="city">Kiel</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schlesner, Matthias" sort="Schlesner, Matthias" uniqKey="Schlesner M" first="Matthias" last="Schlesner">Matthias Schlesner</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schumacher, Ton N" sort="Schumacher, Ton N" uniqKey="Schumacher T" first="Ton N." last="Schumacher">Ton N. Schumacher</name>
<affiliation wicri:level="3">
<nlm:aff id="A44">Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Span, Paul N" sort="Span, Paul N" uniqKey="Span P" first="Paul N." last="Span">Paul N. Span</name>
<affiliation wicri:level="1">
<nlm:aff id="A45">Department of Radiation Oncology and department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen,the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Radiation Oncology and department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Teague, Jon W" sort="Teague, Jon W" uniqKey="Teague J" first="Jon W." last="Teague">Jon W. Teague</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Totoki, Yasushi" sort="Totoki, Yasushi" uniqKey="Totoki Y" first="Yasushi" last="Totoki">Yasushi Totoki</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045</wicri:regionArea>
<wicri:noRegion>104-0045</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tutt, Andrew N J" sort="Tutt, Andrew N J" uniqKey="Tutt A" first="Andrew N. J." last="Tutt">Andrew N. J. Tutt</name>
<affiliation wicri:level="3">
<nlm:aff id="A46">Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Valdes Mas, Rafael" sort="Valdes Mas, Rafael" uniqKey="Valdes Mas R" first="Rafael" last="Valdés-Mas">Rafael Valdés-Mas</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo</wicri:regionArea>
<wicri:noRegion>33006 Oviedo</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Van Buuren, Marit M" sort="Van Buuren, Marit M" uniqKey="Van Buuren M" first="Marit M." last="Van Buuren">Marit M. Van Buuren</name>
<affiliation wicri:level="3">
<nlm:aff id="A44">Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Van Veer, Laura" sort="Van Veer, Laura" uniqKey="Van Veer L" first="Laura" last="Van Veer">Laura Van Veer</name>
<affiliation wicri:level="1">
<nlm:aff id="A47">The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam</wicri:regionArea>
<wicri:noRegion>1066 CX Amsterdam</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vincent Salomon, Anne" sort="Vincent Salomon, Anne" uniqKey="Vincent Salomon A" first="Anne" last="Vincent-Salomon">Anne Vincent-Salomon</name>
<affiliation wicri:level="1">
<nlm:aff id="A48">Institut Curie , Departement de Pathologie, INSERM U830, 26 rue d’Ulm 75248 PARIS CEDEX 05, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Curie , Departement de Pathologie, INSERM U830, 26 rue d’Ulm 75248 PARIS CEDEX 05</wicri:regionArea>
<wicri:noRegion>75248 PARIS CEDEX 05</wicri:noRegion>
<wicri:noRegion>75248 PARIS CEDEX 05</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Waddell, Nicola" sort="Waddell, Nicola" uniqKey="Waddell N" first="Nicola" last="Waddell">Nicola Waddell</name>
<affiliation wicri:level="1">
<nlm:aff id="A38">Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072</wicri:regionArea>
<wicri:noRegion>Queensland 4072</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yates, Lucy R" sort="Yates, Lucy R" uniqKey="Yates L" first="Lucy R." last="Yates">Lucy R. Yates</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Zucman Rossi, Jessica" sort="Zucman Rossi, Jessica" uniqKey="Zucman Rossi J" first="Jessica" last="Zucman-Rossi">Jessica Zucman-Rossi</name>
<affiliation wicri:level="3">
<nlm:aff id="A28">INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A29">Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris-Descartes</orgName>
</affiliation>
</author>
<author>
<name sortKey="Futreal, P Andrew" sort="Futreal, P Andrew" uniqKey="Futreal P" first="P. Andrew" last="Futreal">P. Andrew Futreal</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Mcdermott, Ultan" sort="Mcdermott, Ultan" uniqKey="Mcdermott U" first="Ultan" last="Mcdermott">Ultan Mcdermott</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Lichter, Peter" sort="Lichter, Peter" uniqKey="Lichter P" first="Peter" last="Lichter">Peter Lichter</name>
<affiliation wicri:level="3">
<nlm:aff id="A49">Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Meyerson, Matthew" sort="Meyerson, Matthew" uniqKey="Meyerson M" first="Matthew" last="Meyerson">Matthew Meyerson</name>
<affiliation wicri:level="2">
<nlm:aff id="A30">The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Broad Institute of MIT and Harvard, Cambridge, Massachusetts</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A39">Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A40">Harvard Medical School, Boston, Massachusetts, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Harvard Medical School, Boston, Massachusetts</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Grimmond, Sean M" sort="Grimmond, Sean M" uniqKey="Grimmond S" first="Sean M." last="Grimmond">Sean M. Grimmond</name>
<affiliation wicri:level="1">
<nlm:aff id="A38">Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072</wicri:regionArea>
<wicri:noRegion>Queensland 4072</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Siebert, Reiner" sort="Siebert, Reiner" uniqKey="Siebert R" first="Reiner" last="Siebert">Reiner Siebert</name>
<affiliation wicri:level="3">
<nlm:aff id="A42">Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Human Genetics, Christian-Albrechts-University, Kiel</wicri:regionArea>
<placeName>
<region type="land" nuts="2">Schleswig-Holstein</region>
<settlement type="city">Kiel</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Campo, Elias" sort="Campo, Elias" uniqKey="Campo E" first="Elías" last="Campo">Elías Campo</name>
<affiliation wicri:level="4">
<nlm:aff id="A50">Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Universitat de Barcelona, IDIBAPS, 08036 Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Universitat de Barcelona, IDIBAPS, 08036 Barcelona</wicri:regionArea>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</region>
<settlement type="city">Barcelone</settlement>
</placeName>
<orgName type="university">Université de Barcelone</orgName>
</affiliation>
</author>
<author>
<name sortKey="Shibata, Tatsuhiro" sort="Shibata, Tatsuhiro" uniqKey="Shibata T" first="Tatsuhiro" last="Shibata">Tatsuhiro Shibata</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045</wicri:regionArea>
<wicri:noRegion>104-0045</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Pfister, Stefan M" sort="Pfister, Stefan M" uniqKey="Pfister S" first="Stefan M." last="Pfister">Stefan M. Pfister</name>
<affiliation wicri:level="3">
<nlm:aff id="A27">Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation>
<nlm:aff id="A51">Department of Pediatric Hematology and Oncology, Heidelberg</nlm:aff>
<wicri:noCountry code="subfield">Heidelberg</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J." last="Campbell">Peter J. Campbell</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A12">Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ</wicri:regionArea>
<wicri:noRegion>Cambridge CB2 0QQ</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A13">Department of Haematology, University of Cambridge, Cambridge CB2 2XY, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge CB2 2XY</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name>
<affiliation>
<nlm:aff id="A1">Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</nlm:aff>
<wicri:noCountry code="subfield">CB10 1SA</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Nature</title>
<idno type="ISSN">0028-0836</idno>
<idno type="eISSN">1476-4687</idno>
<imprint>
<date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="P2">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,
<italic>kataegis</italic>
, 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.</p>
</div>
</front>
<back>
<div1 type="bibliography">
<listBibl>
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</author>
<author>
<name sortKey="Futreal, Pa" uniqKey="Futreal P">PA Futreal</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
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<name sortKey="Pfeifer, Gp" uniqKey="Pfeifer G">GP Pfeifer</name>
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<biblStruct>
<analytic>
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<analytic>
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<name sortKey="Welch, Js" uniqKey="Welch J">JS Welch</name>
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<analytic>
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<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">0410462</journal-id>
<journal-id journal-id-type="pubmed-jr-id">6011</journal-id>
<journal-id journal-id-type="nlm-ta">Nature</journal-id>
<journal-id journal-id-type="iso-abbrev">Nature</journal-id>
<journal-title-group>
<journal-title>Nature</journal-title>
</journal-title-group>
<issn pub-type="ppub">0028-0836</issn>
<issn pub-type="epub">1476-4687</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">23945592</article-id>
<article-id pub-id-type="pmc">3776390</article-id>
<article-id pub-id-type="doi">10.1038/nature12477</article-id>
<article-id pub-id-type="manuscript">EMS54099</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Signatures of mutational processes in human cancer</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Alexandrov</surname>
<given-names>Ludmil B.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nik-Zainal</surname>
<given-names>Serena</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wedge</surname>
<given-names>David C.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Aparicio</surname>
<given-names>Samuel A.J.R.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Behjati</surname>
<given-names>Sam</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Biankin</surname>
<given-names>Andrew V.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
<xref ref-type="aff" rid="A10">10</xref>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bignell</surname>
<given-names>Graham R.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bolli</surname>
<given-names>Niccolo</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A12">12</xref>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Borg</surname>
<given-names>Ake</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Børresen-Dale</surname>
<given-names>Anne-Lise</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Boyault</surname>
<given-names>Sandrine</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Burkhardt</surname>
<given-names>Birgit</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Butler</surname>
<given-names>Adam P.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Caldas</surname>
<given-names>Carlos</given-names>
</name>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Davies</surname>
<given-names>Helen R.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Desmedt</surname>
<given-names>Christine</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eils</surname>
<given-names>Roland</given-names>
</name>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Eyfjörd</surname>
<given-names>Jórunn Erla</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Foekens</surname>
<given-names>John A.</given-names>
</name>
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</contrib>
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<given-names>Mel</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Hosoda</surname>
<given-names>Fumie</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Hutter</surname>
<given-names>Barbara</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Ilicic</surname>
<given-names>Tomislav</given-names>
</name>
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</contrib>
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<name>
<surname>Imbeaud</surname>
<given-names>Sandrine</given-names>
</name>
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<given-names>Natalie</given-names>
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</contrib>
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<name>
<surname>Jones</surname>
<given-names>David T.W.</given-names>
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<name>
<surname>Jones</surname>
<given-names>David</given-names>
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<given-names>Carlos</given-names>
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<name>
<surname>Martin</surname>
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<surname>Nakamura</surname>
<given-names>Hiromi</given-names>
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</contrib>
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<surname>Northcott</surname>
<given-names>Paul A.</given-names>
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<given-names>Marina</given-names>
</name>
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</contrib>
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<name>
<surname>Papaemmanuil</surname>
<given-names>Elli</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Paradiso</surname>
<given-names>Angelo</given-names>
</name>
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</contrib>
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<name>
<surname>Pearson</surname>
<given-names>John V.</given-names>
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</contrib>
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<name>
<surname>Puente</surname>
<given-names>Xose S.</given-names>
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<surname>Raine</surname>
<given-names>Keiran</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Ramakrishna</surname>
<given-names>Manasa</given-names>
</name>
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</contrib>
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<given-names>Andrea L.</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Richter</surname>
<given-names>Julia</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Rosenstiel</surname>
<given-names>Philip</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Schlesner</surname>
<given-names>Matthias</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Schumacher</surname>
<given-names>Ton N.</given-names>
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</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Teague</surname>
<given-names>Jon W.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Totoki</surname>
<given-names>Yasushi</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Tutt</surname>
<given-names>Andrew N.J.</given-names>
</name>
<xref ref-type="aff" rid="A46">46</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Valdés-Mas</surname>
<given-names>Rafael</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>van Buuren</surname>
<given-names>Marit M.</given-names>
</name>
<xref ref-type="aff" rid="A44">44</xref>
</contrib>
<contrib contrib-type="author">
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<given-names>Laura</given-names>
</name>
<xref ref-type="aff" rid="A47">47</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vincent-Salomon</surname>
<given-names>Anne</given-names>
</name>
<xref ref-type="aff" rid="A48">48</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Waddell</surname>
<given-names>Nicola</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Yates</surname>
<given-names>Lucy R.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<collab>Australian Pancreatic Cancer Genome Initiative</collab>
</contrib>
<contrib contrib-type="author">
<collab>ICGC Breast Cancer Consortium</collab>
</contrib>
<contrib contrib-type="author">
<collab>ICGC MMML-Seq Consortium</collab>
</contrib>
<contrib contrib-type="author">
<collab>ICGC PedBrain</collab>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zucman-Rossi</surname>
<given-names>Jessica</given-names>
</name>
<xref ref-type="aff" rid="A28">28</xref>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Futreal</surname>
<given-names>P. Andrew</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>McDermott</surname>
<given-names>Ultan</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Lichter</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="A49">49</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Meyerson</surname>
<given-names>Matthew</given-names>
</name>
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<xref ref-type="aff" rid="A39">39</xref>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Grimmond</surname>
<given-names>Sean M.</given-names>
</name>
<xref ref-type="aff" rid="A38">38</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Siebert</surname>
<given-names>Reiner</given-names>
</name>
<xref ref-type="aff" rid="A42">42</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Campo</surname>
<given-names>Elías</given-names>
</name>
<xref ref-type="aff" rid="A50">50</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shibata</surname>
<given-names>Tatsuhiro</given-names>
</name>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Pfister</surname>
<given-names>Stefan M.</given-names>
</name>
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<xref ref-type="aff" rid="A51">51</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Campbell</surname>
<given-names>Peter J.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Stratton</surname>
<given-names>Michael R.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA</aff>
<aff id="A2">
<label>2</label>
Department of Medical Genetics, Box 134, Addenbrooke’s Hospital NHS Trust, Hills Road, Cambridge CB2 0QQ</aff>
<aff id="A3">
<label>3</label>
Molecular Oncology, Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada</aff>
<aff id="A4">
<label>4</label>
Centre for Translational and Applied Genomics, Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada</aff>
<aff id="A5">
<label>5</label>
Department of Pathology, University of British Columbia, G227-2211 Wesbrook Mall, British Columbia, Vancouver V6T 2B5, Canada</aff>
<aff id="A6">
<label>6</label>
Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY</aff>
<aff id="A7">
<label>7</label>
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom.</aff>
<aff id="A8">
<label>8</label>
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland G4 0SF, United Kingdom</aff>
<aff id="A9">
<label>9</label>
The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia</aff>
<aff id="A10">
<label>10</label>
Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia</aff>
<aff id="A11">
<label>11</label>
South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia</aff>
<aff id="A12">
<label>12</label>
Department of Haematology, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK</aff>
<aff id="A13">
<label>13</label>
Department of Haematology, University of Cambridge, Cambridge CB2 2XY, UK</aff>
<aff id="A14">
<label>14</label>
Department of Oncology, Lund University, SE-221 85 Lund, Sweden</aff>
<aff id="A15">
<label>15</label>
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway</aff>
<aff id="A16">
<label>16</label>
The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway</aff>
<aff id="A17">
<label>17</label>
Plateforme de Bioinformatique Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laennec, 69373 LYON CEDEX 08</aff>
<aff id="A18">
<label>18</label>
NHL-BFM Study Center and Department of Pediatric Hematology and Oncology, University Children’s Hospital, Münster, Germany</aff>
<aff id="A19">
<label>19</label>
NHL-BFM Study Center and Department of Pediatric Hematology and Oncology, University Children’s Hospital, Giessen, Germany</aff>
<aff id="A20">
<label>20</label>
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE</aff>
<aff id="A21">
<label>21</label>
Breast Cancer Translational Res Lab - BCTL, Université Libre de Bruxelles - Institut Jules Bordet, Boulevard de Waterloo, 125, B-1000 Brussels</aff>
<aff id="A22">
<label>22</label>
Department of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany</aff>
<aff id="A23">
<label>23</label>
Cancer Research Laboratory, Faculty of Medicine, Biomedical Centre, University of Iceland, 101 Reykjavik, Iceland</aff>
<aff id="A24">
<label>24</label>
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands</aff>
<aff id="A25">
<label>25</label>
Department of Haemato-oncology, Institute of Cancer Research, London</aff>
<aff id="A26">
<label>26</label>
Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan</aff>
<aff id="A27">
<label>27</label>
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany</aff>
<aff id="A28">
<label>28</label>
INSERM, UMR-674, Génomique Fonctionnelle des Tumeurs Solides, Institut Universitaire d’Hematologie (IUH), Paris, France</aff>
<aff id="A29">
<label>29</label>
Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France</aff>
<aff id="A30">
<label>30</label>
The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA</aff>
<aff id="A31">
<label>31</label>
Section of Oncology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway</aff>
<aff id="A32">
<label>32</label>
Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway</aff>
<aff id="A33">
<label>33</label>
The University of Queensland Centre for Clinical Research, School of Medicine and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Herston 4029,Brisbane, QLD, Australia</aff>
<aff id="A34">
<label>34</label>
Dpt. Bioquímica y Biología Molecular, IUOPA-Universidad de Oviedo, 33006 Oviedo, Spain</aff>
<aff id="A35">
<label>35</label>
Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA</aff>
<aff id="A36">
<label>36</label>
Boston Veterans Administration Healthcare System, West Roxbury, MA</aff>
<aff id="A37">
<label>37</label>
Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126, Bari, Italy</aff>
<aff id="A38">
<label>38</label>
Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia</aff>
<aff id="A39">
<label>39</label>
Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA</aff>
<aff id="A40">
<label>40</label>
Harvard Medical School, Boston, Massachusetts, USA</aff>
<aff id="A41">
<label>41</label>
Department of Pathology, Brigham and Women’s Hospital 75 Francis St. Boston, MA 02115, USA</aff>
<aff id="A42">
<label>42</label>
Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany</aff>
<aff id="A43">
<label>43</label>
Institute of Clinical Molecular Biology, Christian-Albrechts-University,Kiel, Germany</aff>
<aff id="A44">
<label>44</label>
Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands</aff>
<aff id="A45">
<label>45</label>
Department of Radiation Oncology and department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen,the Netherlands</aff>
<aff id="A46">
<label>46</label>
Breakthrough Breast Cancer Research Unit, King’s College London School of Medicine, London, UK</aff>
<aff id="A47">
<label>47</label>
The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands</aff>
<aff id="A48">
<label>48</label>
Institut Curie , Departement de Pathologie, INSERM U830, 26 rue d’Ulm 75248 PARIS CEDEX 05, France</aff>
<aff id="A49">
<label>49</label>
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany</aff>
<aff id="A50">
<label>50</label>
Unidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Universitat de Barcelona, IDIBAPS, 08036 Barcelona, Spain</aff>
<aff id="A51">
<label>51</label>
Department of Pediatric Hematology and Oncology, Heidelberg</aff>
<author-notes>
<corresp id="CR1">
<bold>Address for correspondence</bold>
Michael R. Stratton Wellcome Trust Sanger Institute, Hinxton Cambridgeshire CB10 1SA United Kingdom
<email>mrs@sanger.ac.uk</email>
</corresp>
<fn id="FN1">
<p id="P1">
<bold>AUTHOR CONTRIBUTIONS</bold>
L.B.A., S.N.Z., M.R.S. conceptualized the study and analyzed the mutational signatures and
<italic>kataegis</italic>
data. L.B.A. performed data curation, data filtering, and mutational signature extraction. S.N.Z. and D.C.W. performed
<italic>kataegis</italic>
identification. S.N.Z. performed visual validation. A.P.B., K.R., J.W.T., D.J. provided bioinformatics support for mutational signature and
<italic>kataegis</italic>
analysis. S.A.J.R.A., S.B., A.V.B., G.R.B., N.B., A.B., A.L.B.D., S.B., B.B., C.C., H.R.D., C.D., R.E., J.E.E., J.A.F., M.G., F.H., B.H., T.I., S.I., M.I., N.J., D.T.W.J., S.K., M.K., S.R.L., C.L.O., S.M., N.C.M., H.N., P.A.N., M.P., E.P., A.P., J.V.P., X.S.P, M.R., A.L.R., J.R., P.R., M.S., T.N.S., P.N.S., Y.T., A.N.J.T., R.V.M., M.M.B., L.V., A.V.S., N.W., L.R.Y., J.Z.R., P.A.F., U.M., P.L., M.M., S.M.G., R.S., E.C., T.S., S.M.P., P.J.C. contributed samples, clinical data and scientific advice. M.R.S. and L.B.A. wrote the manuscript. M.R.S. directed the overall research.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>9</day>
<month>9</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub">
<day>14</day>
<month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub">
<day>22</day>
<month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>22</day>
<month>2</month>
<year>2014</year>
</pub-date>
<volume>500</volume>
<issue>7463</issue>
<fpage>415</fpage>
<lpage>421</lpage>
<permissions>
<license>
<license-p>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:
<uri xlink:type="simple" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</uri>
</license-p>
</license>
</permissions>
<abstract>
<p id="P2">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,
<italic>kataegis</italic>
, 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.</p>
</abstract>
<funding-group>
<award-group>
<funding-source country="United Kingdom">Wellcome Trust : </funding-source>
<award-id>093867 || WT</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
<floats-group>
<fig id="F1" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<title>The prevalence of somatic mutations across human cancer types</title>
<p>Every dot represents a sample while the red horizontal lines are the median numbers of mutations in the respective cancer types. The vertical axis (log scaled) shows the number of mutations per megabase while the different cancer types are ordered on the horizontal axis based on their median numbers of somatic mutations. We would like to thank Gad Getz and colleagues for the design of this figure
<sup>
<xref ref-type="bibr" rid="R26">26</xref>
</sup>
.</p>
</caption>
<graphic xlink:href="emss-54099-f0001"></graphic>
</fig>
<fig id="F2" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<title>Validated mutational signatures found in human cancer</title>
<p>Each signature is displayed according to the 96 substitution classification defined by the substitution class and sequence context immediately 3′ and 5′ to the mutated base. The probability bars for the six types of substitutions are displayed in different colors. The mutation types are on the horizontal axes, while vertical axes depict the percentage of mutations attributed to a specific mutation type. All mutational signatures are displayed based on the trinucleotide frequency of the human genome. A higher resolution of each panel is found respectively in
<xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 2</xref>
to
<xref ref-type="supplementary-material" rid="SD1">23</xref>
.</p>
</caption>
<graphic xlink:href="emss-54099-f0002"></graphic>
</fig>
<fig id="F3" orientation="portrait" position="float">
<label>Figure 3</label>
<caption>
<title>The presence of mutational signatures across human cancer types</title>
<p>Cancer types are ordered alphabetically as columns while mutational signatures are displayed as rows. “Other” indicates mutational signatures for which we were not able to perform validation or for which validation failed (
<xref ref-type="supplementary-material" rid="SD1">Supplementary Figs 24</xref>
to
<xref ref-type="supplementary-material" rid="SD1">28</xref>
). Prevalence in cancer samples indicates the percentage of samples from our dataset of 7,042 cancers in which the signature contributed significant number of somatic mutations. For most signatures, significant number of mutations in a sample is defined as more than 100 substitutions or more than 25% of all mutations in that sample.</p>
</caption>
<graphic xlink:href="emss-54099-f0003"></graphic>
</fig>
<fig id="F4" orientation="portrait" position="float">
<label>Figure 4</label>
<caption>
<title>The contributions of mutational signatures to individual cancers of selected cancer types</title>
<p>Each bar represents a typical selected sample from the respective cancer type and the vertical axis denotes the number of mutations per megabase. Contributions across all cancer samples could be found in
<xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 29</xref>
to
<xref ref-type="supplementary-material" rid="SD1">58</xref>
. Summary of the total contributions for all operative mutational processes in a cancer type could be found in
<xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 59</xref>
to
<xref ref-type="supplementary-material" rid="SD1">88</xref>
. “Other” indicates mutational signatures for which we were not able to perform validation or for which validation failed (
<xref ref-type="supplementary-material" rid="SD1">Supplementary Figs 24</xref>
to
<xref ref-type="supplementary-material" rid="SD1">28</xref>
).</p>
</caption>
<graphic xlink:href="emss-54099-f0004"></graphic>
</fig>
<fig id="F5" orientation="portrait" position="float">
<label>Figure 5</label>
<caption>
<title>Mutational signatures with strong transcriptional strand bias</title>
<p>Mutations are shown according to the 192 mutation classification incorporating the substitution type, the sequence context immediately 5′ and 3′ to the mutated base and whether the mutated pyrimidine is on the transcribed or untranscribed strand. The mutation types are displayed on the horizontal axis, while the vertical axis depicts the percentage of mutations attributed to a specific mutation type. A higher resolution version of each panel is found respectively in
<xref ref-type="supplementary-material" rid="SD1">Supplementary Figures 89</xref>
to
<xref ref-type="supplementary-material" rid="SD1">95</xref>
.</p>
</caption>
<graphic xlink:href="emss-54099-f0005"></graphic>
</fig>
<fig id="F6" orientation="portrait" position="float">
<label>Figure 6</label>
<caption>
<title>
<italic>Kataegis</italic>
in three cancers</title>
<p>Each of these “rainfall” plots represents an individual cancer sample in which each dot represents a single somatic mutation ordered on the horizontal axis according to its position in the human genome. The vertical axis denotes the genomic distance of each mutation from the previous mutation. Clusters of mutations in
<italic>kataegis</italic>
are arrowed.</p>
</caption>
<graphic xlink:href="emss-54099-f0006"></graphic>
</fig>
</floats-group>
</pmc>
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<list>
<country>
<li>Allemagne</li>
<li>Australie</li>
<li>Belgique</li>
<li>Canada</li>
<li>Espagne</li>
<li>France</li>
<li>Islande</li>
<li>Italie</li>
<li>Japon</li>
<li>Norvège</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>Suède</li>
<li>États-Unis</li>
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<li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Bade-Wurtemberg</li>
<li>Catalogne</li>
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<li>District de Münster</li>
<li>Grand Londres</li>
<li>Gueldre</li>
<li>Hollande-Méridionale</li>
<li>Hollande-Septentrionale</li>
<li>Massachusetts</li>
<li>Rhénanie-du-Nord-Westphalie</li>
<li>Schleswig-Holstein</li>
<li>Écosse</li>
<li>Île-de-France</li>
<li>Østlandet</li>
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<settlement>
<li>Amsterdam</li>
<li>Barcelone</li>
<li>Cambridge</li>
<li>Glasgow</li>
<li>Heidelberg</li>
<li>Kiel</li>
<li>Londres</li>
<li>Münster</li>
<li>Nimègue</li>
<li>Oslo</li>
<li>Paris</li>
<li>Rotterdam</li>
</settlement>
<orgName>
<li>Université Paris-Descartes</li>
<li>Université de Barcelone</li>
<li>Université de Cambridge</li>
<li>Université de Glasgow</li>
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