01147: Identifying Mutations in Genes Associated with Canine Hemangiosarcoma
Grant Status: Closed
Hemangiosarcoma (HSA), a malignant tumor of blood vessels, is a significant health concern in dogs, with a reported incidence of up to 2% of all tumors. HSA can affect all dogs, but a particularly high disease incidence has been reported in certain breeds, such as Golden Retriever (15%), German Shepherd Dog (10%), and Labrador Retriever, suggesting that genetic risk factors exist. We have identified six regions in the canine genome that differ in golden retrievers with and without HSA and verified the findings with more advanced technology in this project. We are currently identifying the actual mutations. So far no mutations in candidate genes have been found, supporting the major role of regulatory mutations. Once the mutation has been found, it will be possible to rapidly develop genetic tests for risk assessment for susceptibility of HSA. Interpretation of these DNA tests will require the consideration of markers for all genes simultaneously as well as assessing risks for different types of cancer. The presence of multiple interacting genes, some at high frequency in the population, will make it difficult to reduce the disease frequency quickly, but should still allow for informed breeding. In addition, by examining the frequency of these mutations in other breeds we can determine which other breeds need to be screened for these mutations and to what degree they contribute to the risk of HSA in specific breeds. Still, perhaps the most significant outcome of knowing the actual mutations is that it might suggest which dogs should be under surveillance or preventive care. The identification of actual mutations should also lead to further study of functional effects of the causative mutations thereby increasing the understanding of the disease mechanism. A better molecular understanding will suggest novel treatment options and possible new drug targets. Due to aggressive nature, HSA is uniquely qualified for studying local invasion, angiogenesis and metastasis, and developing therapeutic intervention in dogs and humans.
>Tonomura, N., Elvers, I., Thomas, R., Megquier, K., Turner-Maier, J., Howald, C., … Lindblad-Toh, K. (2015). Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers. PLOS Genetics, 11(2), e1004922. https://doi.org/10.1371/journal.pgen.1004922
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