00754A: Mapping of the Gene for Transitional Cell Carcinoma in the Scottish Terrier & West Highland White Terrier

Grant Status: Closed

Grant Amount: $102,400.66
Deborah Knapp, DVM; Purdue University
April 1, 2007 - March 31, 2009

Sponsor(s): The Foundation of the Cairn Terrier Club of America

Breed(s): West Highland White Terrier, Scottish Terrier
Research Program Area: Oncology
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Project Summary

We have successfully identified two loci associated with the development of TCC in the three most highly affected dog breeds in the United States. The first locus, which appears to be most highly associated with the disease in STs, has been reduced through fine mapping to two regions comprised of approximately four genes, all of which are fine candidates for enhanced tumor development and progression. We are currently sequencing the genes and searching for the causative mutations. The second locus, which was identified in WHWTs and SSD, may contain a mutation that is fixed or carried at a very high frequency in STs, explaining their increased risk of developing the disease. Studies from human bladder cancer suggest that these two loci may be interacting to create a more aggressive form of bladder cancer in dogs carrying both.

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). 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

Dhawan, D., Ramos-Vara, J. A., Stewart, J. C., Zheng, R., & Knapp, D. W. (2009). Canine invasive transitional cell carcinoma cell lines: In vitro tools to complement a relevant animal model of invasive urinary bladder cancer. Urologic Oncology: Seminars and Original Investigations, 27(3), 284–292. https://doi.org/10.1016/j.urolonc.2008.02.015

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