Discussion This study was able to ascertain c KIT and PDGFRA mutational status of seventeen of eighteen KIT positive canine gastrointestinal stromal tumors, representing a good amplification success rate of 94% from FFPE tis sues. Significantly, the study identified two distinct but overlapping mutations in exon 11 of c KIT in the juxta membrane domain. selleckchem This region appears to be a muta tional hotspot with an overall incidence of 35. 3% in our study population of canine GISTs. The only other study of c KIT mutations in canine GISTs reported mutations in two of four GISTs. Human GISTs have higher incidences of c KIT mutations ranging from 65% to 92% across exons 8, 9, 11, 13, and 17, a majority of which occur in the juxtamembrane domain. In our study, no mutations were identified in exons 8, 9, 13, and 17 of c KIT.

None of our cases showed muta tions in PDGFRA. Only Inhibitors,Modulators,Libraries a single amplification product was noted from the corresponding normal tissue of each Inhibitors,Modulators,Libraries GIST case, with sequencing verifying the presence of only the wild type allele in the normal tissue. These results indicate that all mutations observed arose soma tically in each tumor. Interestingly, these deletion mutations are similar to those previously found in the juxtamembrane domain of c KIT in canine cutaneous mast cell tumors in our laboratory and others. In a previous study of 21 canine GISTs, DNA suitable for amplification was recovered from only four cases and then amplified for the KIT exon 11 of c KIT, juxtamembrane domain, and sequenced.

Sequencing revealed mutations in two of the four canine GISTs, one with a 6 base pair deletion, TGGAAG, and insertion of CAG, predicted to translate to a deletion of tryptophan and lysine and an insertion of glycine at codon 556. This deletion is quite similar to the mutation Inhibitors,Modulators,Libraries at canine Inhibitors,Modulators,Libraries codons 556 557 discovered in the canine GISTs in our study. The second mutation discovered by Frost et al. was a substitution of T with C predicted to replace codon 575 leucine with proline. We did not detect a similar mutation in our study Inhibitors,Modulators,Libraries population. The mutations observed in our study popu lation of GISTs were clustered at codons 556 558 of c KIT. No gender predilection has been reported in human GISTs, and the observation of 73% female to 27% male ratio in our study is interesting, but its signifi cance needs further evaluation.

A simple deletion identical to the mutation at canine codons 556 557 in our study has also been reported in multiple cases of human GISTs. In the study by Taniguchi et al, a deletion and point mutation similar to the mutation at canine codons 556 558 in our study was also detected in one of the cases selleck inhibitor they analyzed. Rubin et al, found the same mutation as the deletion of canine codons 556 557 in our canine GISTs in 2 of 48 human GISTs, and they reported the same deletion of canine codons 556 558 in 1 of the 48 cases.