2010: Dissecting the Biology and Genetics of c-Kit Mutations in Canine Mast Cell Tumors

Grant Status: Closed

Grant Amount: $42,550
Cheryl A. London, DVM, PhD; University of California, Davis
September 26, 2000 - September 30, 2002

Sponsor(s): Chinese Shar-Pei Charitable Trust, Rhodesian Ridgeback Club of the United States, Staffordshire Bull Terrier Club of America

Breed(s): -All Dogs
Research Program Area: Oncology
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The most common malignant tumor in dogs is the mast cell tumor (MCT, a form of skin cancer), occurring with an incidence of close to 20 percent in the canine population. Particular breeds of dog are at risk for the development of this tumor, indicating a role for genetic factors. MCTs range from relatively benign to extremely aggressive, leading to tumor spread and eventual death. Although surgical removal with or without radiation therapy may cure some patients, there are no effective treatments for dogs with aggressive MCTs. We have previously identified mutations in the gene c-kit in several dog MCTs. c-Kit plays a critical role in regulating the growth and function of normal mast cells, and as the mutations we discovered cause uncontrolled function of c-kit, it is likely they influence MCT development in dogs. This research will explore the unique characteristics of the canine genome that lead to such a high frequency of c-kit mutations, as well as investigate the biological effects of such mutations on mast cells. In summary, this work will provide a much more detailed understanding of dog MCTs, thereby building a framework for the development of new therapies and strategies for disease prevention.


Downing, S., Chien, M. B., Kass, P. H., Moore, P. F., & London, C. A. (2002). Prevalence and importance of internal tandem duplications in exons 11 and 12 of c- kit in mast cell tumors of dogs. American Journal of Veterinary Research, 63(12), 1718–1723. https://doi.org/10.2460/ajvr.2002.63.1718

Lin, T.-Y., Fenger, J., Murahari, S., Bear, M. D., Kulp, S. K., Wang, D., … London, C. A. (2010). AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated Kit. Blood, 115(21), 4217–4225. https://doi.org/10.1182/blood-2009-07-231985

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