Mutational Analysis of and in Canine Gastrointestinal Stromal Tumors (GISTs).

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the canine gastrointestinal tract and are diagnosed by the immunohistochemical expression of the receptor tyrosine kinase (RTK) KIT. Activating mutations of the proto-oncogenes and drive GIST oncogenesis and are used to predict the response to RTK-inhibitors in human oncology. Currently, the frequency and significance of these mutations in canine GIST have not been adequately explored. Therefore, we investigated the mutational status of (exons 9, 11 and 13) and (exons 12 and 18) genes by PCR followed by fragment analysis for deletions and PCR followed by screening with DHPLC and direct sequencing confirmation for single nucleotide variations in 17 formalin-fixed paraffin-embedded canine GISTs confirmed by KIT immunopositivity. mutations were detected in 47% of cases, with a mutation detection rate significantly higher ( = 0.0004, Fisher's exact test) and always involving exon 11. A gene mutation (exon 18) was identified in one case. Even if follow-up data were not available for all cases, four cases with documented abdominal metastases displayed mutations. These data confirm that exon 11 mutations occur frequently in canine GISTs, and identify the presence of a mutation similar to human GISTs. This study also suggests a potential association of mutation with more aggressive biological behavior.