01577: Identifying the Genes Conferring Risk for Transitional Cell Carcinoma

Grant Amount: $45,000

Elaine A Ostrander, PhD; National Human Genome Research Institute

January 1, 2012 - June 30, 2014

Sponsor(s): German Shepherd Dog Club of America, Norwegian Elkhound Association of America, Inc., Siberian Husky Club of America, Westie Foundation of America, Inc.,

Breed(s): Shetland Sheepdog, West Highland White Terrier, Scottish Terrier

Research Program Area: Oncology

Abstract

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.

Publication(s)

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