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

Timothy R. Rebbeck*, Tara M. Friebel, Eitan Friedman, Ute Hamann, Dezheng Huo, Ava Kwong, Edith Olah, Olufunmilayo I. Olopade, Angela R. Solano, Soo-Hwang Teo, Mads Thomassen, Jeffrey N. Weitzel, T. L. Chan, Fergus J. Fergus, David E. Goldgar, Torben A. Kruse, Edenir Inez Edenir, Sue Kyung Park, Diana Torres, Elizabeth J. van RensburgLesley McGuffog, Michael T. Parsons, Goska Leslie, Cora M. Aalfs, Julio Abugattas, Julian Adlard, Simona Agata, Kristiina Aittomaki, Lesley Andrews, Irene L. Andrulis, Adalgeir Arason, Norbert Arnold, Banu K. Arun, Ella Asseryanis, Leo Auerbach, Jacopo Azzollini, Judith Balmana, Monica Barile, Rosa B. Barkardottir, Daniel Barrowdale, Javier Benitez, Andreas Berger, Raanan Berger, Amie M. Blanco, Kathleen R. Blazer, Marinus J. Blok, Valerie Bonadona, Bernardo Bonanni, Angela R. Bradbury, Carole Brewer, EMBRACE; GEMO Study Collaborators; HEBON; KConFab Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

150 Citations (Web of Science)

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.
Original languageEnglish
Pages (from-to)593-620
Number of pages28
JournalHuman Mutation
Volume39
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • BRCA1
  • BRCA2
  • breast cancer
  • ethnicity
  • geography
  • mutation
  • ovarian cancer
  • BREAST-CANCER PATIENTS
  • RISK HISPANIC FAMILIES
  • OVARIAN-CANCER
  • GERMLINE MUTATIONS
  • FOUNDER MUTATIONS
  • HAPLOTYPE ANALYSIS
  • HEREDITARY BREAST
  • PHENOTYPE ANALYSIS
  • 185DELAG MUTATION
  • PROSTATE-CANCER

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