Canine intestinal mast cell tumor with c-kit exon 8 mutation responsive to imatinib therapy

A canine intestinal mast cell tumor with splenic metastasis was treated with imatinib. The intestinal and metastatic tumor masses markedly decreased following treatment although the clinical response was short lasting. A c-kit internal tandem duplication mutation, c.1250_1261dup, which causes an insertion of four amino acids in KIT, was identified in cDNA isolated from the tumor cells. The phosphorylation status of the mutant KIT and the effect of imatinib on its phosphorylation were examined using 293 cells transfected with c-kit carrying the c.1250_1261dup mutation. This mutation caused ligand-independent phosphorylation of KIT, which was suppressed by imatinib. Inhibition of constitutively activated mutant KIT with imatinib could underlie the tumor response in this dog.