The Study On The Association Between IDH1 Mutation And HMSH2 Methylation Status In Glioma

Objective:To investigate the relationship between isoctitrate dehydrogenase 1 (isocitrate dehydrogenase IDH1) gene mutation, the state of methylation of glioma mismatch repair genes hMSH2 promoter and the relevance between IDH1 mutation and hMSH2 promoter methylation to furtherly explore the pathogenesis of glioma, in Search of new therapeutic tragets and diagnostic indicators.Methods:Excision of tissue specimens from Neurosurgery, Xiangya Hospital, Central South University were collected in recent 5 months and classfied by pathologist in Xiangya hospital, including 90 cases of brain glioma,4 cases of normal brain tissue,5 cases of meningioma, pituitary adenoma in 5 cases according to WHO classification of brain tumors classification standards; meanwhile peripheral blood of patients weretaken, and the sex, age, previous history of treatment recorded. Blood and tissue DNA were taken direct sequencing after extraction of and polymerase chain amplification (PCR); At the same tiome, The state of the Hmsh2 gene promoter methylation of the specimens were detected with methylation specific PCR(MSP). Analysis and statistical methods used were age, gender, the relationship between the pathological grade, and analysis of IDH1 mutation, hMSH2 promoter methylation Relevance.Results:①There was a total of 43 specimens found IDH1 mutation at codon 132, in 90 cases of gliomas, which took a part of a rate of 47.8%,②There were no mutation in 5 cases of brain glioma on gradeⅠout of 90 cases;③90 cases of gliomas according to WHO classification in IDHI mutations occurred in gradeⅡwere 58.5%(31/53),ⅢGrade 58.3%(7/12) and secondary glioblastomas 42.9%(3/7), primary glioblastoma mutation rate is very low 7.7%(1/13);④IDH1 mutations were not found in normal brain and pituitary tumors, meningiomas;⑤Young patients mutation had a higher rate of IDHI mutations (P<0.05);⑥Normal glioma tissue showed no hMSH2 promoter methylation;⑦There were 42 cases of hMSH2 gene promoter methylation events in 90 cases of brain glioma accounted for 44.7%;⑧There was no significantly correlated between hMSH2 gene promoter methylation and age, gender, pathological grade on statistical analysis;⑨There was a certain correlation between IDH1 gene mutations and state of hMSH2 promoter methylation(p<0.05).Conclusions:1. There are IDH1 gene mutations in patients of human glioma, on gradeⅡ-Ⅳ, characterized by some tissue specificity;2. There are hMSH2 gene promoter methylation in part of the human brain, while no in mormal brain tissue;3. IDH1 mutations are obviously associated with hMSH2 promoter methylation in gliomas, the joint test is advantageous to diagnosis. 4. IDH1 mutations in this study have not yet been reported domestic, IDH1 gene hMSH2 gene mutation and methylation reported no association.