PROGNOSTIC SIGNIFICANCE OF KIT AND PDGFRA MUTATIONS FOR GASTROINTESTINAL STROMAL TUMORS

DOI: https://doi.org/None

I.V. Tsyganova, I.S. Beliakov, O.A. Anurova, N.N. Mazurenko N.N. Blokhin Russian Cancer Research Center, Kashirskoye shosse, 24, Moscow, Russian Federation, 115478

Introduction. Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of GI tract, are characterized by KIT and PDGFRA activating mutations that are predictive factors. KIT and PDGFRA mutations are present in 85% of GISTs and are associated with clinical-morphologic characteristics, GIST clinical behavior and risk of metastases. There is an actual question if the type of mutation has prognostic significance for patient’s outcome. The aim of the study. Evaluation of prognostic significance of different KIT or PDGFRA mutations for GIST patients. Matherial and methods. Analysis of frequency and spectrum of KIT и PDGFRA mutations in tumor DNA and overall survival of 120 GIST patients in the absence of target therapy. Results. Mutations were found in KIT exons 11 (69%) and 9 (12.5%) and in PDGFRA exon 18 (9.2%). In addition the rare mutations were found in KIT exons 13 (2 cases) and 17 (1 case). The higher overall survival was detected in GIST patients with PDGFRA mutations, KIT exon 11 substitutions or wild type GISTs. Patients with KIT exon 11 substitutions or duplications had better survival then with deletions, more over patients with GISTs bearing deletions encompassing KIT codons W557 and/or K558 had higher survival then with deletions of auto phosphorylation sites Y568 and or Y570. The lower survival without target therapy was found in GISTs patients with mutations in KIT exon 9. Conclusions. The obtained results showed the correlation between mutation status of GISTs and patients survival after operation without target therapy that confirmed the oncogene mutations have some prognostic role.
Keywords: 
Key words. GIST, KIT, PDGFRA, mutations, survival, prognosis
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