01336A: Finding the Mutations that Increase Susceptibility to Transitional Cell Carcinoma in the Scottish Terrier, West Highland Terrier, and Shetland Sheepdog

Project Summary

Cancer is a major cause of death in older dogs and treatment of the disease is often ineffective. We wish to identify the causes of cancer in order to learn how to more effectively predict, prevent, and treat the disease. Genetic (heritable) factors are important in development of Transitional cell carcinoma (TCC) of the bladder. Several breeds such as the Scottish terrier, West Highland White terrier, and the Shetland Sheepdog, are at high risk for the disease, and a subset of dogs from each breed are born with errors in critical genes that then predispose them to the disease. Our goal is to determine ways to identify dogs with genetic risk factors for TCC. Dogs at risk could then either enter cancer prevention trials, undergo screening tests for early detection, and in the future, possibly get treated with 'genetic' therapy. Thus far we have found two regions of the canine genome where error-prone genes lie and are able to discern how the genetic errors are similar and different between dogs with TCC and healthy dogs. We narrowed the responsible gene for one region to a few hundred bases in an interval that has only two genes that are excellent candidate genes for cancer development. In the next 6 months, we expect to evaluate effects of candidate mutations on these genes using innovative genomic tools. We are currently working to reduce the second region to a similar size in order to define the risk haplotype and to identify causative genes. Furthermore, methods developed in this effort will translate to other cancer studies underway, and thus offer the potential to help dogs of many breeds.

Publication(s)

Parker, H. G., Shearin, A. L., & Ostrander, E. A. (2010). Man’s Best Friend Becomes Biology’s Best in Show: Genome Analyses in the Domestic Dog. Annual Review of Genetics, 44(1), 309–336. https://doi.org/10.1146/annurev-genet-102808-115200

Shearin, A. L., & Ostrander, E. A. (2010). Leading the way: canine models of genomics and disease. Disease Models & Mechanisms, 3(1–2), 27–34. https://doi.org/10.1242/dmm.004358