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

EMBRACE, GEMO Study Collaborators, HEBON

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 (US)
Pages (from-to)593-620
Number of pages28
JournalHuman Mutation
Volume39
Issue number5
DOIs
StatePublished - May 1 2018

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Mutation
Population
Research Personnel
Germ-Line Mutation
Genetic Testing
Mutation Rate
North America
Databases

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. / EMBRACE; GEMO Study Collaborators; HEBON.

In: Human Mutation, Vol. 39, No. 5, 01.05.2018, p. 593-620.

Research output: Contribution to journalArticle

EMBRACE ; GEMO Study Collaborators ; HEBON. / Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. In: Human Mutation. 2018 ; Vol. 39, No. 5. pp. 593-620.
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