Canine mast cell tumors (MCT) are the most common malignant skin cancers in dogs. A combination of anticancer drugs including vinblastine, prednisone, and tyrosine kinase inhibitors (toceranib and masitinib) along with surgery and/or radiation therapy is commonly used to treat MCT. Chemotherapy can result in unpredictable clinical outcomes in both responses to therapy and drug toxicity. A patient’s variability of genetic polymorphism CYP3A12 enzyme might affect drug metabolism and clinical outcomes. Many single nucleotide polymorphisms (SNPs) at the human CYP3A locus have been characterized. Recent studies have highlighted the potential for CYP3A variation in susceptibility to several common phenotypes, including cancer. The objectives of this study were to analyze the sequencing of the canine CYP3A12 gene (NCBI accession NP_001003340) from thirteen client-owned dogs with MCT (Grade II-III) and to investigate the patterns of sequence variation that related to clinical response to therapy. Fisher’s exact test was used to assess the correlation between SNPs and clinical response. All 13 patients receiving vinblastine showed signs of toxicity, including vomiting, anorexia, and thrombocytopenia. Three sets of point mutations were found in 6 patients with silent (T12574C, n = 1), missense (T12564G, n = 2) with a change in the amino acid (Ile169Leu), and frameshift mutations (Asp153Glufs, n = 3) in the coding sequences. Three of 6 patients that showed missense (n = 1) and frameshift mutations (n = 2) presented with recurrent MCT after vinblastine chemotherapy. This could represent a further step toward predicted the clinical response of anticancer chemotherapy.
Auburn University College of Veterinary Medicine
Friday, June 15
11:00 AM – 11:15 AM
Friday, June 15
11:15 AM – 11:30 AM
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