01577: Identifying the Genes Conferring Risk for Transitional Cell Carcinoma
Grant Status: Closed
Cancer is a major cause of death in older dogs and treatment is often ineffective. Genetic (heritable) factors are important in development of Transitional cell carcinoma (TCC) of the bladder. The Scottish and West Highland White terriers and the Shetland sheepdog are at high risk for TCC, and a subset of dogs of each breed are born with errors in critical genes that predispose them to the disease. Using these breeds as models for genetic risk, Dr. Ostrander will narrow in on two regions of the genome where error-prone genes were discovered and identify the mutation as well as fine map the remaining critical gene. Methods developed in this effort will translate to other cancers and thus have the potential to help dogs of many breeds.
Parker, H. G., Dhawan, D., Harris, A. C., Ramos-Vara, J. A., Davis, B. W., Knapp, D. W., & Ostrander, E. A. (2020). RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors. BMC Cancer, 20(251). https://doi.org/10.1186/s12885-020-06737-0
Decker, B., Parker, H. G., Dhawan, D., Kwon, E. M., Karlins, E., Davis, B. W., … Ostrander, E. A. (2015). Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer--Evidence for a Relevant Model System and Urine-Based Diagnostic Test. Molecular Cancer Research, 13(6), 993–1002. https://doi.org/10.1158/1541-7786.MCR-14-0689
Hahn, N. M., Bonney, P. L., Dhawan, D., Jones, D. R., Balch, C., Guo, Z., … Knapp, D. W. (2012). Subcutaneous 5-Azacitidine Treatment of Naturally Occurring Canine Urothelial Carcinoma: A Novel Epigenetic Approach to Human Urothelial Carcinoma Drug Development. Journal of Urology, 187(1), 302–309. https://doi.org/10.1016/j.juro.2011.09.010
Ostrander, E. A. (2012). Both Ends of the Leash — The Human Links to Good Dogs with Bad Genes. New England Journal of Medicine, 367(7), 636–646. https://doi.org/10.1056/NEJMra1204453
- 00896-A: Phase I Clinical Trial and Pharmacokinetics of Intravesical Mytomycin C (MMC) for the Treatment of Canine Transitional Cell Carcinoma (TC) of the Urinary Bladder
- 00754B: Mapping of the Gene for Transitional Cell Carcinoma in the Scottish Terrier and West Highland White Terrier
Help Future Generations of Dogs
Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.