title: BRCA2 germline mutations in Cypriot patients with familial breast/ovarian cancer.
abstract: Germline mutations in the BRCA2 gene have been shown to be associated with familial female and male breast cancer. Mutations occur throughout the entire coding region of the gene, and there is considerable ethnic and geographical diversity in the deleterious mutations detected in different populations. No data exist on the role of the BRCA2 gene in the Cypriot population. In this study we present the results of characterizing mutations in the BRCA2 gene, in 26 Cypriot families with multiple cases of breast/ovarian cancer. The entire coding region, including splice sites, of BRCA2 were sequenced using cycle sequencing. In total 29 BRCA2 variants were detected which include 3 truncating mutations, 8 missense mutations, 6 polymorphisms and 12 intronic variants. The 3 truncating mutations are frameshift mutation 8984delG (exon 22), and two nonsense mutations, namely C1913X (exon 11) which is a novel mutation, and K3326X (exon 27). It is of interest that frameshift mutation 8984delG was the most frequent, since it was detected in 5 patients from three different families. Among the 6 polymorphisms detected, polymorphism T77T is novel and similarly 4 of the 12 intronic variants were also novel, namely IVS1+8G>A, IVS1-96insA, IVS4+36A>G and IVS11-51G>T. These results show that deleterious BRCA2 mutations, occur at the same frequency, about 20%, in Cypriot families, as that recorded in other European populations. We conclude that the BRCA2 gene plays a significant role in the familial breast cancer phenotype in the Cypriot population.
authors.affiliation: Department of Electron Microscopy and Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjisavvas
authors.forename: Elpida
authors.initials: E
authors.lastname: Charalambous
authors.forename: Adamos
authors.initials: A
authors.lastname: Adamou
authors.forename: Christina G
authors.initials: CG
authors.lastname: Christodoulou
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D003535:Cyprus; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D024522:Genes, BRCA2; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D004273:DNA, Neoplasm; D022821:RNA Splice Sites