A study of lymphoma in Bullmastiff dogs

Abstract

Lymphoma is the most common cancer in Bullmastiffs and Bullmastiff is one of the breeds that are the most predisposed to lymphoma. The investigation of the population and genome started with the notice of high incidence of the disease in Bullmastiffs in Australia. The prominent mortality of certain types of cancers in specific breeds indicated genetic factors devoting to the tumorigenesis. This thesis provides insight into canine lymphoma in terms of genetics and pathology along with a development of a laboratory analysis. Via GWAS, genomic regions were identified on CFA13 and CFA33 that were associated with risk and four potential candidates, proto-oncogene MYC, PVT1, SENP7, and NFkBIZ. All of them were suggested to be involved in the formation of cancers. Among them, MYC was the first one to be recognized and studied for decades. Immunochemistry was used to determine the level of MYC in neoplastic tissues from Bullmastiffs and several canine breeds. Variability of MYC expression was observed, and may prevent its use as a biomarker or a prognostic indicator, but significant quantitative differences warrant further investigation. Nevertheless, the effects exerted by MYC at different levels at each stage of lymphocytes should be further studied as well as networks the functional genes could possibly form. Finally, a simple method for detection of DNA variants using melt-curve analysis was developed. Further refinement of the method would make this useful for identification of Bullmastiffs at risk of developing lymphoma. In summary, this study contributes to the understanding of early-onset lymphoma in Bullmastiffs and may help with future research on canine oncology.