Lymphoma and hemangiosarcoma are major health problems in golden retrievers, causing both suffering and premature death. As part of our ongoing project, Discovery and Characterization of Heritable and Somatic Cancer Mutations in Golden Retrievers, we have identified several regions of the genome that contain genetic heritable risk factors for lymphoma and hemangiosarcoma in Golden Retrievers. We also identified additional somatic mutations in tumors that occur recurrently in both cancers, some of which are linked to duration of remission when treated with standard of care. Our results indicate that a few heritable genetic risk factors account for as much as 50% of the risk for these cancers. These findings offer the potential to develop tests and strategies for DNA tests that can predict risk for individual dogs, as well as to manage risk across the population as a whole. Indeed, both the inherited risk factors and tumor mutations point to pathways that have been implicated in the pathogenesis of LSA and HSA, and thus should inform the development of targeted therapies.
In this proposal we aim to find the precise mutations for the heritable genetic risk factors and to validate markers (mutations) used to determine risk at the heritable loci in a larger independent population of Golden Retrievers from the USA and from Europe in order to develop robust risk prediction tools and an accompanying DNA test. We will identify and characterize tumor mutations and study their relationship to the heritable risk factors, tumor pathogenetic mechanisms, and disease outcome.