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. MCTs range from relatively benign to extremely aggressive tumors, leading to tumor spread and eventual death. Particular breeds of dog are at risk for the development of this tumor, indicating a role for genetic factors. We have previously identified mutations in the gene c-kit in 30-50 percent of 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 proposal will establish a prospective tumor registry of dog MCTs to be used for investigation of the true incidence of c-kit mutations within specific dog breeds. The studies outlined will identify additional genetic mutations present in dog MCTs that in the future will provide a much more detailed understanding of dog MCTs, and thereby build a framework for the development of potential new therapies and strategies for disease prevention.