Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats.
OBJECTIVE
To evaluate splenic mast cell tumors (MCT) of cats for activating mutations in the proto-oncogene c-kit.


METHODS
10 formalin-fixed, paraffin-embedded splenic MCT from cats in the pathology database of the Veterinary Medical Teaching Hospital at the University of California, Davis.


METHODS
Genomic DNA was isolated from tumor specimens, and the polymerase chain reaction (PCR) procedure was performed for exons 11, 12, and 17. The PCR products were analyzed by use of agarose gel electrophoresis and then directly sequenced.


RESULTS
We did not identify mutations in the juxtamembrane domain (encoded by exons 11 and 12) or catalytic domain (encoded by exon 17) of c-kit in any of the splenic MCT specimens.


CONCLUSIONS
Although mutations in the proto-oncogene c-kit occur frequently in naturally developing MCT in dogs and aggressive mastocytosis in humans, the data reported here documented that dysregulation of Kit function through activating mutations is unlikely in splenic MCT of cats. Therapeutic strategies aimed at inhibiting Kit signaling (ie, kinase inhibitors such as imatinib [STl571]) may not be of benefit for the treatment of this disease in cats.
Dank
Gillian
G
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Chien
May B
MB
London
Cheryl A
CA
D000818:Animals; D001483:Base Sequence; D002371:Cat Diseases / Q000201:enzymology / Q000235:genetics*; D002415:Cats; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D012515:Mast-Cell Sarcoma / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000235:genetics*; D012189:Retrospective Studies; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013160:Splenic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit