title: The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry.
abstract: We report the analysis of altogether 1050 suspected hereditary breast/ovarian cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526 tested only for the most common mutations. Of the 119 families with pathogenic mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%) the BRCA1 c.3331_3334del mutation, the former being specific of Portuguese ancestry and the latter showing a founder effect in Portugal. Interestingly, the two most common mutations were found in a significant proportion of the HBOC families with an a priori BRCAPRO mutation probability <10%. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry, even those fulfilling moderately stringent clinical-criteria for genetic testing, should be specifically analyzed for the two most common BRCA1/BRCA2 founder mutations, and we here present a simple method for this first tier test. Screening of the entire coding regions of BRCA1 and BRCA2 should subsequently be offered to those families with a mutation probability ≥10% if none of those founder mutations are found.
authors.affiliation: Department of Genetics.
authors.forename: A
authors.initials: A
authors.lastname: Peixoto
authors.affiliation: Department of Genetics.
authors.forename: C
authors.initials: C
authors.lastname: Santos
authors.affiliation: Department of Genetics.
authors.forename: P
authors.initials: P
authors.lastname: Pinto
authors.affiliation: Department of Genetics.
authors.forename: M
authors.initials: M
authors.lastname: Pinheiro
authors.affiliation: Department of Genetics.
authors.forename: P
authors.initials: P
authors.lastname: Rocha
authors.affiliation: Department of Genetics.
authors.forename: C
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Department of Genetics.
authors.forename: S
authors.initials: S
authors.lastname: Bizarro
authors.affiliation: Department of Genetics.
authors.forename: I
authors.initials: I
authors.lastname: Veiga
authors.affiliation: Department of Genetics.
authors.forename: A S
authors.initials: AS
authors.lastname: Principe
authors.affiliation: Department of Genetics.
authors.forename: S
authors.initials: S
authors.lastname: Maia
authors.affiliation: Department of Surgical Oncology.
authors.forename: F
authors.initials: F
authors.lastname: Castro
authors.affiliation: Department of Medical Oncology.
authors.forename: R
authors.initials: R
authors.lastname: Couto
authors.affiliation: Department of Gynecology, Portuguese Oncology Institute, Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Gouveia
authors.affiliation: Department of Genetics.|Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
authors.forename: M R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D000328:Adult; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011174:Portugal; D044465:White People / Q000235:genetics
keywords: BRCA1/BRCA2 genes; Portuguese ancestry; founder mutations; genetic testing criteria and strategy