title: Cancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families.
abstract: Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported.We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families.
authors.affiliation: Laboratory of Molecular Oncology, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
authors.forename: Sylvia
authors.initials: S
authors.lastname: De Brakeleer
authors.forename: Jacques
authors.initials: J
authors.lastname: De Grève
authors.forename: Remy
authors.initials: R
authors.lastname: Loris
authors.forename: Nicolas
authors.initials: N
authors.lastname: Janin
authors.forename: Willy
authors.initials: W
authors.lastname: Lissens
authors.forename: Erica
authors.initials: E
authors.lastname: Sermijn
authors.forename: Erik
authors.initials: E
authors.lastname: Teugels
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases