%0 Journal Article
%T Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11
%A Emmalena Gregory-Bryson
%A Elizabeth Bartlett
%A Matti Kiupel
%A Schantel Hayes
%A Vilma Yuzbasiyan-Gurkan
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-559
%X Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples.Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA.The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further demonstrates that spontaneously occurring canine GISTs share molecular features with human GISTs and are an appropriate model for human GISTs.Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumors that arise from the wall of the gastrointestinal tract. Gastrointestinal stromal tumors occur in many species including humans, dogs [1-3], and horses [4,5]. GISTs can metastasize to the liver and peritoneal cavity, warranting a very poor prognosis.
%U http://www.biomedcentral.com/1471-2407/10/559