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.

All Wales Medical Genetics Services University Hospital of Wales Cardiff UK

Bâtiment Cheney D Centre Léon Bérard Lyon France

Biomedical Network on Rare Diseases Madrid Spain

Biomedical Sciences Institute University of Porto Porto Portugal

Cancer Genetics and Prevention Program University of California San Francisco San Francisco USA

Cancer Genetics Laboratory Department of Genetics University of Pretoria South Africa

Cancer Genetics Service Division of Medical Oncology National Cancer Centre Singapore Bukit Merah Singapore

Cáncer Hereditario Instituto de Biología y Genética Molecular IBGM Universidad de Valladolid Valladolid Spain

Cancer Research Center Seoul National University Seoul Korea

Cancer Research Initiatives Foundation Sime Darby Medical Centre Subang Jaya Malaysia

Cancer Risk and Prevention Clinic Dana Farber Cancer Institute Boston USA

Center for Clinical Cancer Genetics and Global Health University of Chicago Chicago USA

Center for Familial Breast and Ovarian Cancer Center for Integrated Oncology Medical Faculty University Hospital Cologne Cologne Germany

Center for Genomic Medicine Rigshospitalet University of Copenhagen Copenhagen Denmark

Center for Medical Genetics Ghent University Gent Belgium

Center for Medical Genetics North Shore University Health System Evanston USA

Centre Antoine Lacassagne Nice France

Centre de Lutte Contre le Cancer Georges François Leclerc France and Genomic and Immunotherapy Medical Institute Dijon University Hospital Dijon France

Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Cambridge UK

Centre of Familial Breast and Ovarian Cancer Department of Medical Genetics Institute of Human Genetics University of Würzburg Germany Würzburg

Centro de Cancer de Mama del Hospital Zambrano Hellion Tecnologico de Monterrey San Pedro Garza Garcia Mexico

City of Hope Clinical Cancer Genomics Community Research Network Duarte USA

Clinical Cancer Genetics Program Division of Human Genetics Department of Internal Medicine The Comprehensive Cancer Center The Ohio State University Columbus USA

Clinical Genetics Branch DCEG NCI NIH Bethesda USA

Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK

Clinical Genetics Research Laboratory Dept of Medicine Cancer Biology and Genetics Memorial Sloan Kettering Cancer Center New York USA

Clinical Genetics Research Laboratory Dept of Medicine Memorial Sloan Kettering Cancer Center New York USA

Clinical Genetics Services Dept of Medicine Memorial Sloan Kettering Cancer Center New York USA

Columbus Cancer Council Ohio State University Columbus USA

CRCHU de Quebec oncologie Centre des maladies du sein Deschênes Fabia Hôpital du Saint Sacrement Sainte Foy Canada

Departamento de Investigacion y de Tumores Mamarios del Instituto Nacional de Cancerologia Mexico City Mexico

Département Oncologie Génétique Prévention et Dépistage Institut Paoli Calmettes Marseille Medical School AM University Marseille France

Department of Basic Sciences Shaukat Khanum Memorial Cancer Hospital and Research Centre Lahore Pakistan

Department of Biomedical Science Seoul National University Graduate School Seoul Korea

Department of Breast Medical Oncology and Clinical Cancer Genetics Program University Of Texas MD Anderson Cancer Center Houston USA

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Cancer Prevention and Control Roswell Park Cancer Institute Buffalo USA

Department of Clinical Genetics Aarhus University Hospital Aarhus N Denmark

Department of Clinical Genetics Academic Medical Center Amsterdam The Netherlands

Department of Clinical Genetics Copenhagen Denmark

Department of Clinical Genetics Family Cancer Clinic Erasmus University Medical Center Rotterdam The Netherlands

Department of Clinical Genetics Helsinki University Hospital Helsinki Finland

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands

Department of Clinical Genetics Lund University Hospital Lund Sweden

Department of Clinical Genetics Maastricht University Medical Center Maastricht The Netherlands

Department of Clinical Genetics Odense University Hospital Odense Denmark

Department of Clinical Genetics Royal Devon and Exeter Hospital Exeter UK

Department of Clinical Genetics Sahlgrenska University Hospital Gothenburg Sweden

Department of Clinical Genetics South Glasgow University Hospitals Glasgow UK

Department of Clinical Genetics VU University Medical Center Amsterdam The Netherlands

Department of Dermatology University of Utah School of Medicine Salt Lake City USA

Department of Epidemiology Cancer Prevention Institute of California Fremont USA

Department of Epidemiology Columbia University New York USA

Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland

Department of Genetics Portuguese Oncology Institute of Porto Porto Portugal

Department of Genetics University Medical Center Groningen University Groningen The Netherlands

Department of Gynaecology and Obstetrics Division of Tumor Genetics Klinikum rechts der Isar Technical University Munich Germany

Department of Gynaecology and Obstetrics Ludwig Maximilian University Munich Germany

Department of Gynaecology and Obstetrics University Hospital Düsseldorf Heinrich Heine University Düsseldorf Germany

Department of Gynaecology and Obstetrics University Hospital Ulm Germany

Department of Gynaecology and Oncology Medical University of Vienna Austria

Department of Gynecological Oncology and Clinical Cancer Genetics Program University Of Texas MD Anderson Cancer Center Houston USA

Department of Gynecology and Obstetrics Medical Faculty and University Hospital Carl Gustav Carus Dresden Germany

Department of Gynecology Vilnius University Hospital Santariskiu Clinics Centre of Woman's Health and pathology Vilnius Lithuania

Department of Health Research and Policy and Stanford Cancer Institute Stanford University School of Medicine Stanford USA

Department of Health Sciences Research Mayo Clinic Rochester USA

Department of Health Sciences Research Mayo Clinic Scottsdale USA

Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands

Department of Internal Medicine Division of Oncology University of Kansas Medical Center Westwood USA

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Canada

Department of Laboratory Medicine and Pathology and Health Sciences Research Rochester USA

Department of Medical Genetics University Medical Center Utrecht The Netherlands

Department of Medical Oncology Beth Israel Deaconess Medical Center Massachusetts USA

Department of Medical Oncology Vall d'Hebron University Hospital Barcelona Spain

Department of Medical Sciences University of Turin Turin Italy

Department of Medicine Abramson Cancer Center Perelman School of Medicine at the University of Pennsylvania Philadelphia USA

Department of Medicine Huntsman Cancer Institute Salt Lake City USA

Department of Medicine Magee Womens Hospital University of Pittsburgh School of Medicine Pittsburgh USA

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Molecular Genetics University of Toronto Toronto Canada

Department of Molecular Medicine University La Sapienza and Istituto Pasteur Fondazione Cenci Bolognetti Rome Italy

Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Hospital HUS Finland

Department of Oncology Karolinska University Hospital Stockholm Sweden

Department of Oncology Radiumhemmet and Institution of Oncology and Patology Karolinska University Hospital and Karolinska Institutet Solna Sweden

Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City USA

Department of Population Sciences Beckman Research Institute of City of Hope Duarte USA

Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea

Department of Surgery Daerim St Mary's Hospital Seoul Korea

Department of Surgery National Institute of Oncology Budapest Hungary

Department of Surgery Soonchunhyang University and Seoul Hospital Seoul Korea

Departments of Pediatrics and Medicine Columbia University New York USA

Dept of OB GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Dept of OB GYN Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Division of Cancer Prevention and Genetics Istituto Europeo di Oncologia Milan Italy

Division of Clinical Cancer Genomics City of Hope Cancer Center California USA

Division of Gynecologic Oncology North Shore University Health System University of Chicago Evanston USA

Division of Human Genetics Departments of Internal Medicine and Cancer Biology and Genetics Comprehensive Cancer Center The Ohio State University Columbus USA

Division of Molecular Pathology Department of Pathology Hong Kong Sanatorium and Hospital Happy Valley Hong Kong

Family Cancer Clinic Netherlands Cancer Institute Amsterdam The Netherlands

Fundación Pública Galega de Medicina Xenómica SERGAS Grupo de Medicina Xenómica USC CIBERER IDIS Santiago de Compostela Spain

Genetic Counseling Unit Hereditary Cancer Program IDIBELL Catalan Institute of Oncology CIBERONC Gran Via de l'Hospitalet Barcelona Spain

Genetic Counseling Unit Hereditary Cancer Program IDIBGI Catalan Institute of Oncology Girona Spain

Genetic Epidemiology Laboratory Department of Pathology University of Melbourne Parkville Australia

Genetics and Computational Biology Department QIMR Berghofer Medical Research Institute Brisbane Australia

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

Genomics Center Centre Hospitalier Universitaire de Québec Research Center and Laval University Quebec City Canada

Harvard TH Chan School of Public Health and Dana Farber Cancer Institute Boston USA

Hematology oncology and transfusion medicine center Dept of Molecular and Regenerative Medicine Vilnius University Hospital Santariskiu Clinics Vilnius Lithuania

Hereditary Cancer Clinic Prince of Wales Hospital Randwick Australia

Human Genetics Group and Genotyping Unit Madrid Spain

Human Genetics Group Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid Spain

IFOM The FIRC Institute of Molecular Oncology Milan Italy

Immunology and Molecular Oncology Unit Veneto Institute of Oncology IOV IRCCS Padua Italy

INBIOMED Faculty of Medicine University of Buenos Aires CONICET and CEMIC Department of Clinical Chemistry Medical Direction Buenos Aires Argentina

Inserm U900 Institut Curie PSL Research University Paris France

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Institute of Cell and Molecular Pathology Hannover Medical School Hannover Germany

Institute of Genetic Medicine Centre for Life Newcastle Upon Tyne Hospitals NHS Trust Newcastle upon Tyne UK

Institute of Human Genetics Campus Virchov Klinikum Berlin Germany

Institute of Human Genetics Pontificia Universidad Javeriana Colombia

Institute of Human Genetics Regensburg University Regensburg Germany

Institute of Human Genetics University Hospital Heidelberg Heidelberg Germany

Institute of Human Genetics University Hospital of Schleswig Holstein Kiel Germany

Institute of Human Genetics University Leipzig Leipzig Germany

Institute of Human Genetics University of Münster Münster Germany

Institute of Medical Genetics and Applied Genomics University of Tuebingen Tuebingen Germany

Institute of Oncology Rivka Ziv Medical Center Zefat Israel

Laboratoire de Génétique Chromosomique Hôtel Dieu Centre Hospitalier Chambéry France

Laboratorio de Genética Molecular Servicio de Genética Hospital Universitario Cruces BioCruces Health Research Institute Barakaldo Spain

Laboratory of Cell Biology Department of Pathology hus 9 Landspitali LSH v Hringbraut 101 Reykjavik Iceland and BMC Faculty of Medicine University of Iceland Reykjavik Iceland

Lombardi Comprehensive Cancer Center Georgetown University Washington USA

Lunenfeld Tanenbaum Research Institute Toronto Canada

Magee Womens Hospital University of Pittsburgh School of Medicine Pittsburgh USA

Medical Director Center for Medical Genetics NorthShore University HealthSystem Clinical Assistant Professor of Medicine University of Chicago Pritzker School of Medicine Evanston USA

Medical Genetics Unit University of London St George's UK

Molecular Diagnostic Unit Hereditary Cancer Program ICO IDIBELL Barcelona Spain

Molecular Diagnostics Laboratory INRASTES National Centre for Scientific Research Demokritos Athens Greece

Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany

Molecular Oncology Laboratory Hospital Clinico San Carlos Instituto de Investigación Sanitaria San Carlos Madrid Spain

Molecular Oncology Research Center Barretos Cancer Hospital São Paulo Brazil

N N Petrov Institute of Oncology St Petersburg Russia

National Human Genome Research Institute National Institutes of Health Bethesda USA

North East Thames Regional Genetics Service Great Ormond Street Hospital for Children NHS Trust London UK

Nottingham Clinical Genetics Service Nottingham University Hospitals NHS Trust Nottingham UK

NRG Oncology Statistics and Data Management Center Roswell Park Cancer Institute Buffalo USA

Oncogenetics Department Barretos Cancer Hospital Barretos Brazil

Oncogenetics Group Vall d'Hebron Institute of Oncology Clinical and Molecular Genetics Area Vall d'Hebron University Hospital Barcelona Spain

Oncogenetics Team The Institute of Cancer Research and Royal Marsden NHS Foundation Trust London UK

Oncogénétique Institut Bergonié Bordeaux France

Ontario Cancer Genetics Network Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital Toronto Canada

Oxford Regional Genetics Service Churchill Hospital Oxford UK

Parkville Familial Cancer Centre Peter MacCallum Cancer Centre Melbourne Australia

Parkville Familial Cancer Centre Royal Melbourne Hospital Melbourne Australia

Program in Cancer Genetics Departments of Human Genetics and Oncology McGill University Montreal Canada

Research Department Peter MacCallum Cancer Centre Melbourne Victoria Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne Parkville Australia

Research Division Peter MacCallum Cancer Centre Melbourne Australia

School of Women's and Children's Health UNSW Sydney Australia

Section of Molecular Diagnostics Department of Biochemistry Aalborg University Hospital Aalborg Denmark

Section of Molecular Genetics Dept of Laboratory Medicine University Hospital of Pisa Pisa Italy

Service de Génétique Clinique Chromosomique et Moléculaire Hôpital Nord St Etienne France

Service de Génétique Institut Curie 26 rue d'Ulm Paris France

Service Régional Oncogénétique Poitou Charentes Centre Hospitalier Niort France

Servicio de Genética CIBERER U705 Hospital de la Santa Creu i Sant Pau Barcelona Spain

Sheffield Clinical Genetics Service Sheffield Children's Hospital Sheffield UK

The Feinstein Institute for Medical Research Manhasset USA

The Gyneco Oncology Department Chaim Sheba Medical Center Ramat Gan Israel

The Hong Kong Hereditary Breast Cancer Family Registry Cancer Genetics Center Hong Kong Sanatorium and Hospital Hong Kong China

The Institute of Oncology Chaim Sheba Medical Center Ramat Gan Israel

The Kinghorn Cancer Centre Garvan Institute of Medical Research Sydney Australia

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

UCLA Schools of Medicine and Public Health Division of Cancer Prevention and Control Research Jonsson Comprehensive Cancer Center Los Angeles USA

UCSF Cancer Genetics and Prevention Program San Francisco USA

Unit of Hereditary Cancer Department of Epidemiology Prevention and Special Functions IRCCS AOU San Martino IST Istituto Nazionale per la Ricerca sul Cancro Genoa Italy

Unit of Medical Genetics Department of Biomedical Experimental and Clinical Sciences University of Florence Florence Italy

Unit of Medical Genetics Department of Medical Oncology and Hematology Fondazione IRCCS Milan Italy

Unit of Molecular Bases of Genetic Risk and Genetic Testing Department of Research Fondazione IRCCS Milan Italy

Unité d'Oncogénétique CHU Arnaud de Villeneuve Montpellier France

Unité d'oncogénétique ICO Centre René Gauducheau Saint Herblain France

Unité de Prévention et d'Epidémiologie Génétique Centre Léon Bérard 28 rue Laënnec Lyon France

Vilnius university Santariskiu hospital National Center of Pathology Vilnius Lithuania

West Midlands Regional Genetics Service Birmingham Women's Hospital Healthcare NHS Trust Edgbaston UK

Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles USA

Yorkshire Regional Genetics Service Chapel Allerton Hospital Leeds UK

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Targeting Oncogenic Pathways in the Era of Personalized Oncology: A Systemic Analysis Reveals Highly Mutated Signaling Pathways in Cancer Patients and Potential Therapeutic Targets