KIT mutations in mast cell tumours from cheetahs (Acinonyx jubatus) and domestic cats (Felis catus)

Abstract

Mast cell tumours (MCT) have been documented in numerous species and mutations within the KIT proto‐oncogene are implicated in the neoplastic biology of mast cells in humans, dogs and cats. This study determined high KIT gene nucleotide and Kit amino acid sequence homology between several species known to suffer mast cell neoplasia and especially high sequence conservation between the cheetah (Acinonyx jubatus) and domestic cat (Felis catus) KIT sequences. As a result, we hypothesised that KIT mutations would exist in the neoplastic DNA of four cheetahs diagnosed with MCT from a recent case series. PCR and Sanger sequencing identified conservative exon 6 KIT mutations in two of the four cheetahs. The mutations were different between the two cheetahs. Only wild‐type DNA in exons 6, 8, 9 and 11 of KIT was observed in the MCTs of the remaining two cheetahs. Twenty cutaneous MCTs from domestic cats were collected for KIT mutation comparison. Twelve tumours possessed a mutation within KIT exons 6, 8 or 9 (60%, 95% CI 38.5%‐81.5%). No mutations were detected in exon 11. There was no significant association between domestic feline MCT KIT mutation status and tumour histological grade (traditional schematic, P = .934; Sabattini 2‐tier schematic, P = .762) or mitotic index (P = .750). KIT mRNA and Kit protein sequences are conserved across species but the role of KIT in feline MCT pathogenesis is not completely understood.

A Scoping Review on Tyrosine Kinase Inhibitors in Cats: Current Evidence and Future Directions

“…This could involve larger-scale studies with a diverse population of MCT cases to validate the association between cytoplasmic KIT expression and prognosis. Mutations in the c-kit gene are present in a significant percentage of feline MCTs [17,19,20,63,65,67,74], but their association with survival has not yet been proven [65]. The future research could focus on understanding the specific types and frequencies of c-kit mutations in feline MCTs and their correlation with clinical outcomes.…”

“…Mutations in the c-kit proto-oncogene, which encodes RTK KIT, were identified in exons 6, 8, 9, 10, 11 and 18 [17,19,20,63,65,67,74,75]. The reported rate of c-kit mutations ranges from 56-68%.…”

“…However, the inconsistent association between aberrant KIT protein localization and c-kit mutations suggests the possibility of yet undiscovered driver mutations in the c-kit gene [63]. For now, various functional mutations have been identified in exons 8, 9, and possibly 10, while the impact of mutations in exons 6 and 11 on KIT protein activity have not been explicitly investigated [17,19,20,63,74]. Interestingly, a suppressive mutation has been found in exon 18.…”