The role of mutational analysis of KIT and PDGFRA in gastrointestinal stromal tumors in a clinical setting

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Most GIST harbor a mutation affecting either the KIT or PDGFRA genes, whereas a small subgroup of tumors is wild type for mutations. Mutation of tyrosine kinase receptors is a mechanism of drug resistance that can occur either at the beginning of treatment (primary resistance) or during the course of therapy (secondary resistance). In addition, mutational status can predict the response to treatment with tyrosine kinase inhibitors, but the role of mutational status as a prognostic factor remains controversial. Evidence of a potential role of mutational status as a prognostic factor has emerged over the past decade. The presence of KIT exon 11 insertion/deletion involving either one or both Trp557-Lys558 amino acids correlates with a poorer clinical outcome if compared to patients with tumors wild type for KIT exon 11 mutations. A malignant clinical behavior has also been documented for KIT exon 13 and KIT exon 9 mutant GIST. Patients with GIST harboring a PDGFRA mutation seem to have a better prognosis than the others. The aim of this paper is to review the clinical significance of tyrosine kinase mutational status.