Analysis Of C-kit And PDGFR? Gene Mutation And Prognosis In Multiple Primary Gastrointestinal Stromal Tumors

Object: To investigate the characteristics of c-kit and PDGFR? gene mutations in multiple primary GISTs;to investigate the presence of different mutations in different tumors;to explore the prognostic factors of multiple primary GIST.Methods:A total of 167 paraffin specimens from 60 patients with multiple primary gastrointestinal stromal tumors were accrued from the Union Hospital of Fujian Medical University from December 2008 to March 2015.Using direct sequencing method to detect the characteristics of C-Kit gene exon 9,11,13,17 and PDGFR? exon12,18 mutations.The relationship between the chi-square test gene mutation and the clinical characteristics of the patient's sex,age,tumor location,tumor size,cell morphology,nuclear division number and risk classification were analyzed by Kaplan-Meier method.Results: None of the 60 patients with multiple primary GIST had different types of mutations in each tumor,and all patients had monoclonal properties.A total of 53 cases(88.3%)of C-kit gene mutations and 7 cases(11.7%)of wild type were detected in 60 cases,and no PDGFR? gene mutation was detected.In the C-kit gene mutation,exon 11 mutation was the most common,46 cases were positive(86.8%,46/53),exon 9 mutation positive in 7 cases(13.2%,7/53).,followed by point mutations in 8 cases(17.4%,8/46),complex mutations(point mutations with deletion mutations)in 3 cases(6.5%,3/46),and the main mutation type of C-kit exon 11 mutation was 35(76.1%,35/46);deletion mutations occurred mainly at the 5 'end of exon 11,concentrated in the 550-576 codon region,the so-called "hot zone",including lysine(Lys)Glutamine(Gln)deletion of codon No.550-556 of 6 amino acids,deletion of codon 570-575 encoding tyrosine(Tyr)to glutamine(Gln)5 amino acids,coding tyrosine(Tyr)To threonine(Ser)6 amino acids of the 568-574 codon deletion and other mutations.And the point mutation is mainly V560 D,that is,GTT mutation to GAT,resulting in the encoded valine(Val)into aspartic acid(Asp).C-kit exon 9 mutations were positive in 7 cases(13.2%,7/53),all of which were codon 502 and 503 codons containing alanine(Ala)and tyrosine(Try)(GCCTAT).No C-kit exon 13 and C-kit exon 17 were detected.There was no significant relationship between the mutation rate and the sex,age,tumor size,nuclear division number,tumor necrosis and risk grading.PFS had no significant relationship with the sex,age,number of mitotic and tumor necrosis of the patients,but was related to the tumor cell morphology,risk grading,tumor size,tumor location and other factors.There was a significant difference in PFS between C-kit exon 11 mutant and C-kit exon 9 mutant group and C-kit exon 11 in different mutation types.Conclusion: 1.Different tumors in multiple primary GIST have the same type of gene mutation,are monoclonal.2.Most of the multiple primary GISTs present C-kit mutations,small in wild type,without PDGFR? mutations.3.Multiple primary GIST,tumor cell morphology,risk grading,tumor size,tumor location,gene mutation type and other factors associated with the prognosis of patients.Similar to the prognostic factors of single GIST.