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Mammary tumors are the most common neoplasm of both women and female unspayed canines, and between them, these tumors show a high degree of histological similarity. Up to ten percent of mammary tumors in women are of a familial, inherited nature. Certain breeds of dogs have also shown a predisposition to mammary tumors, suggesting a genetic component to the neoplastic process. This breed predisposition also appears to extend to males. Data from the Veterinary Medical Database demonstrates that male Cocker Spaniels have 4.5 times the risk of mammary cancer than male dogs in general. Genes that have been shown to cause inherited susceptibility to mammary cancer in humans include BRCA1 and BRCA2, and the only gene associated with mammary cancer in men is BRCA2. We hypothesized, therefore, that BRCA2 may play a role in the susceptibility of Cocker Spaniels, particularly males, to mammary cancer. PCR primer pairs were developed to amplify all 26 exons of BRCA2 as well as intron-exon boundaries. To date, BRCA2 has been sequenced in one male affected Cocker Spaniel. There do not appear to be any significant SNPs in the sequence of this single dog. We will be examining sequence data from other affected and unaffected cocker spaniels. Additionally, primers for microsatellite markers near and within both BRCA1 and BRCA2 gene loci have been identified and will be used to genotype a population of affected Cocker Spaniels (male and female) and their tumors. This data will be examined for loss of heterozygosity and allelic imbalance.
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