1. Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- Author
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John W.M. Martens, Sandrine Boyault, David Jones, Stefania Tommasi, Jeong-Yeon Lee, Germán Fg Rodríguez-González, Inigo Martincorena, Sung-Min Ahn, Alastair M Thompson, Manasa Ramakrishna, Gilles Thomas, Helen Davies, Savitri Krishnamurthy, Stian Knappskog, Steven Van Laere, Lucy Stebbings, Andrea L. Richardson, Andrew Tutt, Anne Lise Børresen-Dale, Olafur Oa Stefansson, Sunil R. Lakhani, Michiel M. Smid, Gerrit Gk Hooijer, Young Seok Ju, Tari Ta King, Rebecca Shepherd, Luc Dirix, Xavier Pivot, Adam Butler, Aquila Fatima, Peter Pt Simpson, Serena Nik-Zainal, Sancha Martin, Hyung-Yong Kim, Hendrik G. Stunnenberg, Jos Jonkers, Michael R. Stratton, Jon W. Teague, Se Jin Jang, Sandro Morganella, Ville Mustonen, Moritz Gerstung, Gu Kong, Carlos Caldas, Anne Vincent-Salomon, Anieta M. Sieuwerts, Lucy R. Yates, Sarah O’Meara, Peter B. Vermeulen, Dominik Glodzik, Peter Van Loo, Naoto T. Ueno, Arie B. Brinkman, Stuart McLaren, Yang Li, Marc J. van de Vijver, Laura Van't Veer, P. Andrew Futreal, Markus Ringnér, Christos Sotiriou, Ewan Birney, Kamna Ramakrishnan, Miriam Ragle Aure, Johan Staaf, Jane E. Brock, Benita Kiat Tee Bk Tan, Alain Viari, Xueqing Zou, Anita Langerød, David C. Wedge, Hee Jin Lee, Christine Desmedt, Gilles Romieu, Paul N. Span, Jorunn E. Eyfjord, Annegien Broeks, Isabelle Treilleux, Åke Borg, Colin Ca Purdie, Ole Christian Lingjærde, Gert Van den Eynden, John A. Foekens, Serge Dronov, Andrew Menzies, Peter J. Campbell, Iris Pauporté, Ludmil B. Alexandrov, Keiran Raine, The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Radboud university [Nijmegen], Oslo University Hospital Radiumhospitalet, University of Oslo (UiO), Gachon University Hospital, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Brigham and Women's Hospital [Boston], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Algemeen Ziekenhuis St Augustinus Oncology, Dana-Farber Cancer Institute [Boston], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of Ulsan, NASA Johnson Space Center (JSC), NASA, University of Stuttgart, Esso UK Ltd, Department of Exploration, Esso UK Ltd, Department of Computer Science & Engineering [Riverside] (CSE), University of California [Riverside] (UCR), University of California-University of California, Department of Geriatric Medicine [Singapore] (Alexandra Hospital), Institut national du cancer [Boulogne] (INCA), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Department of Pathology [Dundee], Ninewells Hospital and Medical School [Dundee], Canary Institute for Cancer Research (ICIC), Department of Biochemistry and Physiology, Faculty of Health Sciences, University of Las Palmas de Gran Canaria (ULPGC), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Medical Oncology [Rotterdam], Cancer Genomics Centre, University of Queensland [Brisbane], University of Iceland [Reykjavik], Beckman Research Institute [Duarte, CA], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Antwerp (UA), European Central Bank (ECB), European Central Bank, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Tumor Biology, Institut Curie [Paris], University of Cambridge [UK] (CAM), Division of Diagnostic Oncology, Netherlands Cancer Institute, Agendia BV, Breakthrough Breast Cancer Centre, London Institute of Cancer, University of Bergen (UiB), National Cancer Centre Singapore (NCCS), National Cancer Centre Singapore, Division of Molecular Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies, Baobab, Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Department of Radiation Oncology 874, Radboud University Medical Center [Nijmegen], Department of Laboratory Medicine, Department Medical Oncology, Department of Pathology, Ospedale 'Mater Salutis', Goddard Earth Sciences and Technology and Research (GESTAR), NASA-Universities Space Research Association (USRA), Department of Molecular Biology [Nijmegen], Department of Organismic and Evolutionary Biology [Cambridge] (OEB), Harvard University [Cambridge], Department of Computing [London], Biomedical Image Analysis Group [London] (BioMedIA), Imperial College London-Imperial College London, Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Sagot, Marie-France, Radboud University [Nijmegen], University of California [Riverside] (UC Riverside), University of California (UC)-University of California (UC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nik-Zainal, Serena [0000-0001-5054-1727], Zou, Xueqing [0000-0003-1143-1028], Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository, Medical Oncology, Harvard University, Fondation Synergie Lyon Cancer [Lyon], CCA -Cancer Center Amsterdam, Pathology, Erasmus University Medical Center [Rotterdam], University of Oslo ( UiO ), Genomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Netherlands Cancer Institute ( NKI ), Institut Jules Bordet, Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ), NASA Johnson Space Center ( JSC ), Department of Computer Science & Engineering [Riverside] ( CSE ), University of California [Riverside] ( UCR ), Institut national du cancer [Boulogne] ( INCA ), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Department of Medical Oncology, Erasmus Medical Center Rotterdam, Josephine Nefkens Institute and Cancer Genomics Centre, University of Las Palmas de Gran Canaria ( ULPGC ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Erasmus MC, Beckman Research Institute, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Antwerp ( UA ), European Central Bank ( ECB ), U 830, Institut National de la Santé et de la Recherche Médicale, Institut Curie, University of Cambridge [UK] ( CAM ), University of Bergen ( UIB ), National Cancer Centre Singapore ( NCCS ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale ( ERABLE ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Goddard Earth Sciences and Technology and Research ( GESTAR ), NASA-Universities Space Research Association ( USRA ), Department of Organismic and Evolutionary Biology ( OEB ), and Biomedical Image Analysis Group [London] ( BioMedIA )
- Subjects
0301 basic medicine ,DNA Replication ,Male ,Mutation rate ,DNA repair ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Genes, BRCA2 ,Genes, BRCA1 ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Genome ,Cohort Studies ,03 medical and health sciences ,Germline mutation ,SDG 3 - Good Health and Well-being ,Mutation Rate ,medicine ,Humans ,Gene ,Molecular Biology ,Genetics ,Mutation ,Multidisciplinary ,[ SDV ] Life Sciences [q-bio] ,Genome, Human ,Recombinational DNA Repair ,DNA, Neoplasm ,Genomics ,Oncogenes ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,3. Good health ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Mutagenesis ,Human genome ,Female ,Engineering sciences. Technology - Abstract
Item does not contain fulltext We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
- Published
- 2016
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