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

emBRAce, GEMO Study Collaborators, HEBON

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)593-620
Number of pages28
JournalHuman Mutation
Issue number5
StatePublished - May 2018


FundersFunder number
Autonomous Government of CataloniaRD12/0036/008, ISCIIIRETIC RD06/0020/1051, PI10/00748, 2014SGR364
BBMRI12-054, 184.021.007/CP46
Barretos Cancer Hospital
Cancer Councils of New South Wales
Cancer Foundation of Western Australia
Cancer Research Initiatives Foundation
Department of DefenceW81XWH-10-1-0341
Dutch Cancer SocietyNKI1998-1854, NKI2004-3088, NKI2007-3756
Entertainment Industry Fund National Women's Cancer Research Alliance
European Regional Development FEDER
Finnish Cancer Society
Fiorgen Foundation for PharmacogenomicsIG2015, 16732
French National Institute of Cancer
Genome Québec
Helsinki University Hospital
Hereditary Cancer Research Registry
Hungarian Research Grants KTIA-OTKACK-80745, NKFIH/ OTKA K-112228
Icelandic Association
Instituto Nacional del Cancer
Israeli Inherited breast cancer consortium
MMCIMEYS-NPS ILO1413, 00209805
Malaysian Ministry of Science, Technology and Innovation
Ministero della Salute and “5 × 1000” Istituto Oncologico Veneto
Ministry of Economy, Science and Innovation
Ministry of Health Health Services Research Grant Singapore and Lee Foundation
Ministry of University and Research
Morris and Horowitz Families Endowed
NRG Oncology OperationsU10 CA180868
NRG SDMCCA 37517, CA 27469, U10 CA180822
National Institute of Health
National Medical Research Council of Singapore
National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea1020350, 1420190
National Strategic Reference FrameworkSYN11_10_19 NBCA
Netherlands Organisation of Scientific Research2014-187, 110005, NWO 91109024
Norwegian EEA Financial Mechanism Hu0115/NA/2008
Ohio State University Comprehensive Cancer Center
Queensland Cancer Fund
Robert and Kate Niehaus Clinical Cancer Genetics Initiative
Russian Federation for Basic Research15-04-01744, 14-04-93959
Sigrid Juselius Foundation
Spanish Health Research Fund
Spanish Ministry of Economy and Competitiveness
Spanish Ministry of HealthPI16/00440
Swing Fore the Cure
US National Cancer Institute
USA National Cancer Institute
University of Kansas Cancer Center5U01CA113916, R01CA140323, P30 CA168524
National Institutes of Health1U19 CA148537, CA176785, R25CA171998, CA116167, NO2-CP-11019-50, 1U19 CA148112, N02-CP-65504, 1U19 CA148065, CA128978
National Institutes of Health
American Cancer SocietySIOP-06-258-06-COUN
American Cancer Society
National Cancer InstituteCA116201, R01 CA142996, 1U01CA161032, CA125183
National Cancer Institute
Office of the Director
Susan G. Komen for the Cure
Breast Cancer Research FoundationRC4CA153828
Breast Cancer Research Foundation
Ovarian Cancer Research Fund
ITT Corporation
National Center for Advancing Translational SciencesUL1TR000124
National Center for Advancing Translational Sciences
National Institute on Handicapped Research
Jess and Mildred Fisher Center for Familial Cancer Research
Univerzita Karlova v PrazeUNCE204024
Univerzita Karlova v Praze
Fundación Mutua Madrileña
Georgetown University
Dr. Ralph and Marian Falk Medical Research Trust
German Cancer Research Center
Genome Canada
David F. and Margaret T. Grohne Family Foundation
Ministère du Développement Économique, de l’Innovation et de l’ExportationPSR-SIIRI-701
Ministère du Développement Économique, de l’Innovation et de l’Exportation
College of Environmental Science and Forestry, State University of New York
Andrew Sabin Family Foundation
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchC5047/A8385
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
Fondation du cancer du sein du Québec
Rare Diseases Clinical Research Network
Government of Canada
Canadian Institutes of Health Research019511, CRN-87521
Canadian Institutes of Health Research
Cancer Research UKC5047/A10692, C5047/A8384, C1287/A11990, C1287/A 10710, C1287/A10118, C1281/A12014, C5047/A15007, C8197/A16565
Cancer Research UK
European Commission
National Health and Medical Research Council
National Breast Cancer Foundation
Cancer Australia
Cancer Association of South Africa
Fundação de Amparo à Pesquisa do Estado de São Paulo2013/24633-2
Fundação de Amparo à Pesquisa do Estado de São Paulo
Academy of Finland266528
Academy of Finland
Ministry of Higher EducationUM.C/HlR/MOHE/06, UM.C/HIR/MOHE/06
Ministry of Higher Education
Fundación Científica Asociación Española Contra el Cáncer
Consejo Nacional de Investigaciones Científicas y Técnicas
Ministerio de Economía y CompetitividadSAF2014-57680-R
Ministerio de Economía y Competitividad
Ministério da Ciência, Tecnologia e Inovação
Israel Cancer Association
Istituto Toscano Tumori
Ligue Contre le Cancer
Landspítali Háskólasjúkrahús
Lietuvos Mokslo TarybaSEN-18/2015
Lietuvos Mokslo Taryba
Instituto de Salud Carlos III
Istituto Pasteur-Fondazione Cenci Bolognetti
Financiadora de Estudos e Projetos02/2010
Financiadora de Estudos e Projetos
European Social Fund
Seventh Framework Programme223175
Seventh Framework Programme
Associazione Italiana per la Ricerca sul CancroIG2014, 15547, IG17734
Associazione Italiana per la Ricerca sul Cancro
Deutsche Krebshilfe110837
Deutsche Krebshilfe
European Regional Development FundPI10/01422, PI13/00285, PI15/00854, PI16/00563, PIE13/00022
European Regional Development Fund
Pontificia Universidad Javeriana
Liga Portuguesa Contra o Cancro
Institut Català de la Salut2014SGR338, 2009SGR290
Institut Català de la Salut
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"5 × 1000′
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
Ministerio de Defensa, Argentina


    • BRCA1
    • BRCA2
    • breast cancer
    • ethnicity
    • geography
    • mutation
    • ovarian cancer


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