Fulltext

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Rebbeck TR 1 , Friebel TM 1 , Friedman E 2 , Hamann U 3 , Huo D 4 , Kwong A 5 Show all authors , Olah E 6 , Olopade OI 4 , Solano AR 7 , Teo SH 8 , Thomassen M 9 , Weitzel JN 10 , Chan TL 11 , Couch FJ 12 , Goldgar DE 13 , Kruse TA 9 , Palmero EI 14 , Park SK 15 , Torres D 3 , van Rensburg EJ 16 , McGuffog L 17 , Parsons MT 18 , Leslie G 17 , Aalfs CM 19 , Abugattas J 20 , Adlard J 21 , Agata S 22 , Aittomäki K 23 , Andrews L 24 , Andrulis IL 25 , Arason A 26 , Arnold N 27 , Arun BK 28 , Asseryanis E 29 , Auerbach L 29 , Azzollini J 30 , Balmaña J 31 , Barile M 32 , Barkardottir RB 26 , Barrowdale D 17 , Benitez J 33 , Berger A 34 , Berger R 35 , Blanco AM 36 , Blazer KR 10 , Blok MJ 37 , Bonadona V 38 , Bonanni B 32 , Bradbury AR 39 , Brewer C 40 , Buecher B 41 , Buys SS 42 , Caldes T 43 , Caliebe A 44 , Caligo MA 45 , Campbell I 46 , Caputo SM 41 , Chiquette J 47 , Chung WK 48 , Claes KBM 49 , Collée JM 50 , Cook J 51 , Davidson R 52 , de la Hoya M 43 , De Leeneer K 49 , de Pauw A 41 , Delnatte C 53 , Diez O 54 , Ding YC 55 , Ditsch N 56 , Domchek SM 39 , Dorfling CM 16 , Velazquez C 57 , Dworniczak B 58 , Eason J 59 , Easton DF 17 , Eeles R 60 , Ehrencrona H 61 , Ejlertsen B 62 , EMBRACE 17 , Engel C 63 , Engert S 64 , Evans DG 65 , Faivre L 66 , Feliubadaló L 67 , Ferrer SF 68 , Foretova L 69 , Fowler J 70 , Frost D 17 , Galvão HCR 71 , Ganz PA 72 , Garber J 73 , Gauthier-Villars M 41 , Gehrig A 74 , GEMO Study Collaborators 75 , Gerdes AM 76 , Gesta P 77 , Giannini G 78 , Giraud S 79 , Glendon G 80 , Godwin AK 81 , Greene MH 82 , Gronwald J 83 , Gutierrez-Barrera A 28 , Hahnen E 84 , Hauke J 84 , HEBON 85 , Henderson A 86 , Hentschel J 87 , Hogervorst FBL 88 , Honisch E 89 , Imyanitov EN 90 , Isaacs C 91 , Izatt L 92 , Izquierdo A 93 , Jakubowska A 83 , James P 94 , Janavicius R 95 , Jensen UB 96 , John EM 97 , Vijai J 98 , Kaczmarek K 83 , Karlan BY 99 , Kast K 100 , Investigators K 101 , Kim SW 102 , Konstantopoulou I 103 , Korach J 104 , Laitman Y 2 , Lasa A 105 , Lasset C 38 , Lázaro C 67 , Lee A 106 , Lee MH 107 , Lester J 99 , Lesueur F 108 , Liljegren A 109 , Lindor NM 110 , Longy M 111 , Loud JT 82 , Lu KH 112 , Lubinski J 83 , Machackova E 69 , Manoukian S 30 , Mari V 113 , Martínez-Bouzas C 114 , Matrai Z 115 , Mebirouk N 108 , Meijers-Heijboer HEJ 116 , Meindl A 64 , Mensenkamp AR 117 , Mickys U 118 , Miller A 119 , Montagna M 22 , Moysich KB 120 , Mulligan AM 121 , Musinsky J 98 , Neuhausen SL 55 , Nevanlinna H 122 , Ngeow J 123 , Nguyen HP 124 , Niederacher D 89 , Nielsen HR 9 , Nielsen FC 125 , Nussbaum RL 126 , Offit K 127 , Öfverholm A 128 , Ong KR 129 , Osorio A 130 , Papi L 131 , Papp J 6 , Pasini B 132 , Pedersen IS 133 , Peixoto A 134 , Peruga N 83 , Peterlongo P 135 , Pohl E 84 , Pradhan N 98 , Prajzendanc K 83 , Prieur F 136 , Pujol P 137 , Radice P 138 , Ramus SJ 139 , Rantala J 140 , Rashid MU 3 , Rhiem K 84 , Robson M 141 , Rodriguez GC 142 , Rogers MT 143 , Rudaitis V 144 , Schmidt AY 125 , Schmutzler RK 84 , Senter L 145 , Shah PD 39 , Sharma P 146 , Side LE 147 , Simard J 148 , Singer CF 29 , Skytte AB 96 , Slavin TP 10 , Snape K 149 , Sobol H 150 , Southey M 150 , Steele L 55 , Steinemann D 151 , Sukiennicki G 83 , Sutter C 152 , Szabo CI 153 , Tan YY 34 , Teixeira MR 134 , Terry MB 154 , Teulé A 155 , Thomas A 156 , Thull DL 157 , Tischkowitz M 158 , Tognazzo S 22 , Toland AE 159 , Topka S 98 , Trainer AH 160 , Tung N 161 , van Asperen CJ 162 , van der Hout AH 163 , van der Kolk LE 88 , van der Luijt RB 164 , Van Heetvelde M 49 , Varesco L 165 , Varon-Mateeva R 166 , Vega A 167 , Villarreal-Garza C 168 , von Wachenfeldt A 169 , Walker L 170 , Wang-Gohrke S 171 , Wappenschmidt B 84 , Weber BHF 172 , Yannoukakos D 103 , Yoon SY 8 , Zanzottera C 30 , Zidan J 173 , Zorn KK 174 , Hutten Selkirk CG 175 , Hulick PJ 176 , Chenevix-Trench G 18 , Spurdle AB 18 , Antoniou AC 17 , Nathanson KL 39

Affiliations 

  • 1 Harvard TH Chan School of Public Health and Dana Farber Cancer Institute, Boston, USA
  • 2 The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  • 3 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 4 Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, USA
  • 5 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China
  • 6 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
  • 7 INBIOMED, Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry, Medical Direction, Buenos Aires, Argentina
  • 8 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
  • 9 Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
  • 10 Division of Clinical Cancer Genomics, City of Hope Cancer Center, California, USA
  • 11 Division of Molecular Pathology, Department of Pathology, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong
  • 12 Department of Laboratory Medicine and Pathology, and Health Sciences Research, Rochester, USA
  • 13 Department of Dermatology, University of Utah School of Medicine, Salt Lake City, USA
  • 14 Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
  • 15 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 16 Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, South Africa
  • 17 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 18 Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 19 Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
  • 20 City of Hope Clinical Cancer Genomics Community Research Network, Duarte, USA
  • 21 Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK
  • 22 Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
  • 23 Department of Clinical Genetics, Helsinki University Hospital, Helsinki, Finland
  • 24 Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, Australia
  • 25 Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
  • 26 Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • 27 Department of Gynaecology & Oncology, Medical University of Vienna, Austria
  • 28 Department of Breast Medical Oncology and Clinical Cancer Genetics Program, University Of Texas MD Anderson Cancer Center, Houston, USA
  • 29 Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • 30 Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT), Milan, Italy
  • 31 Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
  • 32 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy
  • 33 Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • 34 Dept of OB/GYN, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • 35 The Institute of Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel
  • 36 UCSF Cancer Genetics and Prevention Program, San Francisco, USA
  • 37 Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands
  • 38 Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, 28 rue Laënnec, Lyon, France
  • 39 Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
  • 40 Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK
  • 41 Service de Génétique, Institut Curie, 26 rue d'Ulm, Paris, France
  • 42 Department of Medicine, Huntsman Cancer Institute, Salt Lake City, USA
  • 43 Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
  • 44 Institute of Human Genetics, University Hospital of Schleswig-Holstein, Kiel, Germany
  • 45 Section of Molecular Genetics, Dept. of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy
  • 46 Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia
  • 47 CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia, Hôpital du Saint-Sacrement, Sainte-Foy, Canada
  • 48 Departments of Pediatrics and Medicine, Columbia University, New York, USA
  • 49 Center for Medical Genetics, Ghent University, Gent, Belgium
  • 50 Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 51 Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK
  • 52 Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow, UK
  • 53 Unité d'oncogénétique, ICO-Centre René Gauducheau, Saint Herblain, France
  • 54 Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area, Vall d'Hebron University Hospital, Barcelona, Spain
  • 55 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, USA
  • 56 Department of Gynaecology and Obstetrics, Ludwig-Maximilian University, Munich, Germany
  • 57 Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM, Universidad de Valladolid, Valladolid, Spain
  • 58 Institute of Human Genetics, University of Münster, Münster, Germany
  • 59 Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK
  • 60 Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK
  • 61 Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
  • 62 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 63 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
  • 64 Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University, Munich, Germany
  • 65 Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  • 66 Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute, Dijon University Hospital, Dijon, France
  • 67 Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute), Barcelona, Spain
  • 68 Laboratoire de Génétique Chromosomique, Hôtel Dieu Centre Hospitalier, Chambéry, France
  • 69 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • 70 Columbus Cancer Council, Ohio State University, Columbus, USA
  • 71 Oncogenetics Department, Barretos Cancer Hospital, Barretos, Brazil
  • 72 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, USA
  • 73 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, USA
  • 74 Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics, University of Würzburg, Germany, Würzburg
  • 75 Department of Tumour Biology, Institut Curie, Paris, France
  • 76 Department of Clinical Genetics, Copenhagen, Denmark
  • 77 Service Régional Oncogénétique Poitou-Charentes, Centre Hospitalier, Niort, France
  • 78 Department of Molecular Medicine, University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti, Rome, Italy
  • 79 Bâtiment Cheney D, Centre Léon Bérard, Lyon, France
  • 80 Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
  • 81 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, USA
  • 82 Clinical Genetics Branch, DCEG, NCI, NIH, Bethesda, USA
  • 83 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 84 Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany
  • 85 The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 86 Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
  • 87 Institute of Human Genetics, University Leipzig, Leipzig, Germany
  • 88 Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 89 Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University, Düsseldorf, Germany
  • 90 N.N. Petrov Institute of Oncology, St. Petersburg, Russia
  • 91 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, USA
  • 92 Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, UK
  • 93 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona), Catalan Institute of Oncology, Girona, Spain
  • 94 Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Australia
  • 95 Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania
  • 96 Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, Denmark
  • 97 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, USA
  • 98 Clinical Genetics Research Laboratory, Dept. of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
  • 99 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA
  • 100 Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Dresden, Germany
  • 101 Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne, Parkville, Australia
  • 102 Department of Surgery, Daerim St. Mary's Hospital, Seoul, Korea
  • 103 Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology), National Centre for Scientific Research "Demokritos", Athens, Greece
  • 104 The Gyneco-Oncology Department, Chaim Sheba Medical Center, Ramat Gan, Israel
  • 105 Servicio de Genética-CIBERER U705, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • 106 The Feinstein Institute for Medical Research, Manhasset, USA
  • 107 Department of Surgery, Soonchunhyang University and Seoul Hospital, Seoul, Korea
  • 108 Inserm U900, Institut Curie, PSL Research University, Paris, France
  • 109 Department of Oncology Radiumhemmet and Institution of Oncology and Patology, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden
  • 110 Department of Health Sciences Research, Mayo Clinic, Scottsdale, USA
  • 111 Oncogénétique, Institut Bergonié, Bordeaux, France
  • 112 Department of Gynecological Oncology and Clinical Cancer Genetics Program, University Of Texas MD Anderson Cancer Center, Houston, USA
  • 113 Centre Antoine Lacassagne, Nice, France
  • 114 Laboratorio de Genética Molecular, Servicio de Genética, Hospital Universitario Cruces, BioCruces Health Research Institute, Barakaldo, Spain
  • 115 Department of Surgery, National Institute of Oncology, Budapest, Hungary
  • 116 Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
  • 117 Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
  • 118 Vilnius university Santariskiu hospital, National Center of Pathology, Vilnius, Lithuania
  • 119 NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, USA
  • 120 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, USA
  • 121 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
  • 122 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, HUS, Finland
  • 123 Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre Singapore, Bukit Merah, Singapore
  • 124 Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany
  • 125 Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • 126 Cancer Genetics and Prevention Program, University of California San Francisco, San Francisco, USA
  • 127 Clinical Genetics Research Laboratory, Dept. of Medicine, Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, USA
  • 128 Department of Clinical Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 129 West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, UK
  • 130 Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain
  • 131 Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
  • 132 Department of Medical Sciences, University of Turin, Turin, Italy
  • 133 Section of Molecular Diagnostics, Department of Biochemistry, Aalborg University Hospital, Aalborg, Denmark
  • 134 Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
  • 135 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
  • 136 Service de Génétique Clinique Chromosomique et Moléculaire, Hôpital Nord, St Etienne, France
  • 137 Unité d'Oncogénétique, CHU Arnaud de Villeneuve, Montpellier, France
  • 138 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT), Milan, Italy
  • 139 School of Women's and Children's Health, UNSW, Sydney, Australia
  • 140 Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
  • 141 Clinical Genetics Services, Dept. of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA
  • 142 Division of Gynecologic Oncology, North Shore University Health System, University of Chicago, Evanston, USA
  • 143 All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK
  • 144 Department of Gynecology, Vilnius University Hospital Santariskiu Clinics, Centre of Woman's Health and pathology, Vilnius, Lithuania
  • 145 Clinical Cancer Genetics Program, Division of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, USA
  • 146 Department of Internal Medicine, Division of Oncology, University of Kansas Medical Center, Westwood, USA
  • 147 North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, UK
  • 148 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, Canada
  • 149 Medical Genetics Unit, University of London, St George's, UK
  • 150 Département Oncologie Génétique, Prévention et Dépistage, Institut Paoli-Calmettes, Marseille Medical School-AM University, Marseille, France
  • 151 Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany
  • 152 Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
  • 153 National Human Genome Research Institute, National Institutes of Health, Bethesda, USA
  • 154 Department of Epidemiology, Columbia University, New York, USA
  • 155 Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Gran Via de l'Hospitalet, Barcelona, Spain
  • 156 Department of Health Sciences Research, Mayo Clinic, Rochester, USA
  • 157 Department of Medicine, Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, USA
  • 158 Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, Canada
  • 159 Division of Human Genetics, Departments of Internal Medicine and Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, USA
  • 160 Parkville Familial Cancer Centre, Royal Melbourne Hospital, Melbourne, Australia
  • 161 Department of Medical Oncology, Beth Israel Deaconess Medical Center, Massachusetts, USA
  • 162 Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
  • 163 Department of Genetics, University Medical Center, Groningen University, Groningen, The Netherlands
  • 164 Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands
  • 165 Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
  • 166 Institute of Human Genetics, Campus Virchov Klinikum, Berlin, Germany
  • 167 Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain
  • 168 Departamento de Investigacion y de Tumores Mamarios del, Instituto Nacional de Cancerologia, Mexico City, Mexico
  • 169 Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
  • 170 Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK
  • 171 Department of Gynaecology and Obstetrics, University Hospital, Ulm, Germany
  • 172 Institute of Human Genetics, Regensburg University, Regensburg, Germany
  • 173 Institute of Oncology, Rivka Ziv Medical Center, Zefat, Israel
  • 174 Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, USA
  • 175 Center for Medical Genetics, North Shore University Health System, Evanston, USA
  • 176 Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine, University of Chicago Pritzker School of Medicine, Evanston, USA
Hum Mutat, 2018 05;39(5):593-620.
PMID: 29446198 DOI: 10.1002/humu.23406

Abstract

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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