title: Novel BRCA1/2 mutations in Serbian breast and breast-ovarian cancer patients with hereditary predisposition.
abstract: Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. The study was designed to detect mutational spectra of BRCA1/2 genes in a Serbian population. Using automated DNA sequencing, we tested individuals for BRCA mutations, based on positive family history of either breast or ovarian cancer or both. Two novel mutations (c.4765_4784del in BRCA1 exon 15 and c.4367_4368dupTT in BRCA2 exon 11) were detected, in three probands from two different families. These mutations have not been reported previously in the BIC or LOVD databases. Protein products of these mutated alleles lack domains necessary for their DNA repair functions, an indicator that these are deleterious mutations. Neither mutation was found in any proband from 50 other families with hereditary predisposition, so the two mutations are likely family-specific rather than population-specific. Although BRCA1-associated tumors are typically negative for estrogen receptor (ER), progesterone receptor (PR), and ERBB2, the novel BRCA1 mutation identified in this study was detected in a proband with ER- and PR-positive breast cancer. Steroid receptor-positive BRCA-related breast cancer in this proband supports the idea of characteristic pathological features and older age of onset among BRCA1-mutated ER-positive breast cancers.
authors.affiliation: Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. jelena.dobricic@ncrc.ac.rs
authors.forename: Jelena
authors.initials: J
authors.lastname: Dobricić
authors.forename: Mirjana
authors.initials: M
authors.lastname: Branković-Magić
authors.forename: Slađana
authors.initials: S
authors.lastname: Filipović
authors.forename: Sinisa
authors.initials: S
authors.lastname: Radulović
mesh_terms: D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D055771:Serbia
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone