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

Grant Status: Closed

Grant Amount: $70,000
Elaine A Ostrander, PhD; National Human Genome Research Institute
April 1, 2007 - March 31, 2009

Sponsor(s): Pug Dog Club of America, Inc., Samoyed Club of America Education & Research Foundation

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)

Cadieu, E., & Ostrander, E. A. (2007). Canine Genetics Offers New Mechanisms for the Study of Human Cancer. Cancer Epidemiology Biomarkers & Prevention, 16(11), 2181–2183. https://doi.org/10.1158/1055-9965.EPI-07-2667
 
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
 
Fleischer, S., Sharkey, M., Mealey, K., Ostrander, E. A., & Martinez, M. (2008). Pharmacogenetic and Metabolic Differences Between Dog Breeds: Their Impact on Canine Medicine and the Use of the Dog as a Preclinical Animal Model. The AAPS Journal, 10(1), 110–119. https://doi.org/10.1208/s12248-008-9011-1
 
Quignon, P., Herbin, L., Cadieu, E., Kirkness, E. F., Hédan, B., Mosher, D. S., … Hitte, C. (2007). Canine Population Structure: Assessment and Impact of Intra-Breed Stratification on SNP-Based Association Studies. PLoS ONE, 2(12), e1324. https://doi.org/10.1371/journal.pone.0001324
 
Wayne, R. K., & Ostrander, E. A. (2007). Lessons learned from the dog genome. Trends in Genetics, 23(11), 557–567. https://doi.org/10.1016/j.tig.2007.08.013

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