Activating mutations in c-KIT and PDGFRα are exclusively found in gastrointestinal stromal tumors and not in other tumors overexpressing these imatinib mesylate target genes
2005
Previous studies have shown that Imatinib mesylate (Gleevec), a selective tyrosine kinase inhibitor of c-KIT and platelet-derived growth factor receptors (PDGFR), is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumors (GIST), especially in those having activating mutations in c-kit exon 11. In addition, gain-of-function mutations in the juxtamembrane domain (exon 12) and the kinase activation loop (exon 18) of PDGFRα were found in GISTs. Importantly, the presence and type of these mutually exclusive c-KIT or PDGFRα mutations were found to be associated with the response to imatinib. Here, we examined the prevalence of c-kit exon 11 and PDGFRα exons 12 and 18 mutations in other tumor types known to express these tyrosine kinase receptors in order to explore which other cancer types may potentially benefit from imatinib treatment. We determined the mutational status of these commonly mutated exons by direct sequencing in 11 different tumor types (in total: 215 unrelated cases), includin...
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