Gastrointestinal stromal tümörlerde kit mutasyonlarinin klinik önemi

The KIT gene exon 9, 11, 13 and 17 activation mutations are associated with clinical behaviour in GIST?s where biological behaviour is highly variable. The purpose of this study is to associate the KIT gene exon 9, 11, 13 and 17 mutations in the GIST?s with histopathologic features and treatment results for the first time in the Turkish population.Sixty-five patients, who were diagnosed as GIST?s, were included to the study. The tumour DNA was sequenced for KIT gene exons 9, 11, 13 and 17 mutations.KIT mutations occurred 8.3% in exon 9, 47.5% in exon 11, 11.7% in exon 13 and 1.7% in exon 17. In our group, certain mutations were identified which were not published in the literature previously.Multivariate analyses indicated an association of malignant potential with a presence of KIT mutations (OR:3.18). It was shown that wild-type patients had 11-fold greater risk of malignant potential when compared to those with mutations in codon W557- K558 (OR:11).All cases and metastatic GIST?s who were under imatinib treatment with exon 11 and KIT mutations have shown significant prolonged survival than wild type cases.Mutant patients benefited more than two fold from imatinib treatment when compared with wild-type (OR:2). Our results suggest that localized GIST?s with KIT mutations may be good candidates for adjuvant therapy with imatinib.Redefining the molecular features associated with tumour behaviour is important for finding new diagnostic or predictive biomarkers in GIST?s.New molecular biomarkers associated with tumour behaviour will provide better management of disease and create new therapeutic targets.Keywords: Gastrointestinal stromal tumors, KIT gene mutations, DNA sequencing, Pharmacogenomic, Biomarker.