Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors.
BACKGROUND
Mutations in the c-KIT proto-oncogene have been implicated in the progression of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and cutaneous mast cell tumors (MCTs) in canines. Mutations in human mastocytosis patients primarily occur in c-KIT exon 17, which encodes a portion of its kinase domain. In contrast, deletions and internal tandem duplication (ITD) mutations are found in the juxtamembrane domain of c-KIT in approximately 15% of canine MCTs. In addition, ITD c-KIT mutations are significantly associated with aberrant KIT protein localization in canine MCTs. However, some canine MCTs have aberrant KIT localization but lack ITD c-KIT mutations, suggesting that other mutations or other factors may be responsible for aberrant KIT localization in these tumors.


METHODS
In order to characterize the prevalence of mutations in the phospho-transferase portion of c-KIT's kinase domain in canine MCTs exons 16-20 of 33 canine MCTs from 33 dogs were amplified and sequenced. Additionally, in order to determine if mutations in c-KIT exon 17 are responsible for aberrant KIT localization in MCTs that lack juxtamembrane domain c-KIT mutations, c-KIT exon 17 was amplified and sequenced from 18 canine MCTs that showed an aberrant KIT localization pattern but did not have ITD c-KIT mutations.


RESULTS
No mutations or polymorphisms were identified in exons 16-20 of any of the MCTs examined.


CONCLUSIONS
In conclusion, mutations in the phospho-transferase portion of c-KIT's kinase domain do not play an important role in the progression of canine cutaneous MCTs, or in the aberrant localization of KIT in canine MCTs.
Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA. webste28@cvm.msu.edu
Joshua D
JD
Webster
Matti
M
Kiupel
Vilma
V
Yuzbasiyan-Gurkan
D000818:Animals; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004283:Dog Diseases / Q000201:enzymology*; D004285:Dogs; D005091:Exons / Q000235:genetics; D005260:Female; D008297:Male; D012515:Mast-Cell Sarcoma / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary / Q000235:genetics; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000235:genetics*; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit