Detection Of The C-kit And PDGFRα Gene Mutation And It's Clinical Significance In Gastrointestinal Stromal Tumors(GISTs)

Objective:To study the mutation of c-kit and PDGFRαgene in gastrointestinal stromal tumors(GIST) and their possible relationship with primary tumor site,clinicalpathologic characteristics and prognosis.Methods:In 50 cases of GIST exon 9,11,13 of c-kit gene and exon 12,18 of PDGFRαgene were sequenced by PCR amplification to analyze the rule of gene mutation in GIST.Based on patient's clinical pathologic features and the follow up data.the relationship between clinicalpathologic characteristics and prognosis and gene mutation was discussed.Results:Among 50 case of GIST mutations of c-kit exone 11 were identified in 60%(30/50),including 15 cases of point mutation in-frame deletion,11 case of in-frame deletion and 4 case of insert duplications.These mutations mostly were clustered in 550-560,the "hot spots" area at the 5' end of the exon 11.the second "hot spot" was internal tandem duplications(ITD) at the 3' end of the exon.PDGFRαmutations were identified in 11.1%of no-c-kit-mutation GISTs and the 50%(2/4)of CD117 negative GISTs,involving exon 18 with mutations D842V and exon 12 with mutation S566I.The overall mutation rate and c-kit exon 11 mutation rate in the GIST originated from stomach was higher than that from small intestinal,colorectum and extra-gastrointestinal tract.The difference is significant(χ~2=5.061,P=0.024;χ~2=7.346,P=0.007),(χ~2=4.20,P=0.04; χ~2=8.75,P =0.013).Mutation rate was higher in the GIST of spindle cell type than that of the epitheloid and mixed cell type.The difference is significant,(χ~2=8.324,P=0.016;χ~2=6.380,P=0.041).The overall mutation rate or c-kit exon 11 mutation rate,was not significant of different between the groups of age,gender,tumor size,grade of malignant potential.Conclusion:1.c-kit mutation presents in most of the GIST.PDGFRαmutation was detected in some GIST without c-kit mutations.2.c-kit gene mutations mainly concentrated in the exon 11 The most commen type of mutation was point mutation,followed by deletion, insertion of tandem repeats.3.c-kit mutation was higher in gastric than that in small intestine, colorectal,and extra-gastrointestinal tract.4.c-kit mutation on the exon 11 was higher in the spindle cell type of GIST than that of the epitheloid and mixed-cell type.5.The presence of c-kit gene mutation is not a significant prognostic factor.