Single nucleotide variation in exon 11 of canine BRCA2 in healthy and cancerous mammary tissue

Abstract

Germline mutations in the BRCA2 tumour suppressor gene are significant risk indicators of breast cancer in women, especially for hereditary breast cancer. The BRCA2 protein interacts via the BRC (breast cancer) domain with RAD51, an essential component of the cellular machinery for the maintenance of genome stability and double strand-breaks repair. Exon 11 is the largest exon of the BRCA2 gene and contains the region encoding eight repeats of the BRC domain. Little is known about the roles of BRCA2 exon 11 in canine mammary tumours. In present study, the entire BRCA2 exon 11 was sequenced in canine mammary tumours. Fifteen mammary gland samples were obtained from four normal mammary glands and 11 mammary tumours (10 malignant and one benign tumours). Comparing sequences of normal mammary glands with those in GenBank (AB043895 and Z75664), a single nucleotide polymorphism (SNP) at codon 2414 G>A (resulting in a lysine to an arginine substitution) was identified. When compared with the normal mammary gland, 19 sporadically distributed point mutations were found in mammary tumours, including 68% of missense and 32% of silent mutations. A high frequency of genetic variations in codon 511 A>C or 2414 A>G were identified in 6/11 cases, and two missense mutations (2414 A>G, 2383 A>C) were located at the fourth repeat of the BRC domains.