title: Founder mutations in BRCA1 and BRCA2 genes.
abstract: BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive from an older or more recent single mutational event or whether they have arisen independently more than once. Here, we review some of the most well-known and significant examples of founder mutations in BRCA genes found in European and non-European populations. In conclusion, the identification of the ethnic group of families undergoing genetic counseling enables the geneticist and oncologist to make more specific choices, leading to simplify the clinical approach to genetic testing carried out on members of high-risk families. Futhermore, the high frequency of founder mutations, allowing to analyze a large number of cases, might provide accurate information regarding their penetrance.
authors.affiliation: Department of Surgery and Oncology, Regional Reference Center for the Biomolecular Characterization and Genetic Screening of Hereditary Tumors, Università di Palermo, Palermo.
authors.forename: R
authors.initials: R
authors.lastname: Ferla
authors.forename: V
authors.initials: V
authors.lastname: Calò
authors.forename: S
authors.initials: S
authors.lastname: Cascio
authors.forename: G
authors.initials: G
authors.lastname: Rinaldi
authors.forename: G
authors.initials: G
authors.lastname: Badalamenti
authors.forename: I
authors.initials: I
authors.lastname: Carreca
authors.forename: E
authors.initials: E
authors.lastname: Surmacz
authors.forename: G
authors.initials: G
authors.lastname: Colucci
authors.forename: V
authors.initials: V
authors.lastname: Bazan
authors.forename: A
authors.initials: A
authors.lastname: Russo
mesh_terms: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D018703:Founder Effect; D005820:Genetic Testing; D006801:Humans; D009154:Mutation
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human