| Summary: | 碩士 === 中興大學 === 獸醫學系暨研究所 === 95 === Mammary gland tumors (MGT) are caused by a complex combination of genetic and environmental factors. Several genes are known to be involvid in human breast cancer. Mutated forms of BRCA1 and BRCA2 are found in 40% of families with histories of early onset breast cancer and ovarian cancer.
BRCA2 plays an essential role in the repair of double-strand DNA breaks via BRC repeats in exon 11 to regulate the action of the RAD51 recombinase. Loss of RAD51 function would result in accumulation of DNA damage and thus would increase the risk of cancer. In the mouse model, the deletion of several BRC repeats has been shown to lead to cancer, but the role of BRCA2 in canine MGT carcinogenesis remains unclear .
In this study, the nucleotide sequences of exon 11, the largest exon of BRCA2 gene, form several canine MGTs were analyzed. Samples, including 4 normal canine breast tissue samples and 11 MGT samples, were obtained from Veterinary Medicine Teaching Hospital of National Chung-Hsing University. Exon 11, consisting of 4521 base pairs, was amplified from genomic DNA isolated from mammary gland tissue by polymerase chain reaction, and the authenticity of resulting products was determined by DNA sequencing. We compared our sequences with published sequences from GenBank (accession No. Z75664) and (accession No. AB043895), and found one nucleotide variation G2414A (Arg805Lys) existing in all mammary gland samples we analyzed, form both normal and MGT specimens. Moreover, in MGT samples, 19 signal nucleotide polymorphisms (SNPs), widely distributed in BRCA2 exon 11, were found and silent mutations and missence mutations constituted 31.5 % and 68.5 % of those SNPs, respectively. Most interestingly, point mutations at nucleotide 511 and 2414 existed in 6 out of 11 samples (54.5 %), whereas other mutations were found in 1/11 (9.1 %) of MGT samples. Further studies are required for elucidating the significance of those mutations of BRCA2 exon 11 in canine MGT carcinogenesis.
|
|---|
