Idh1 Mutations And Dna Methylation Regulation And Stem Cell Gene Expression. Human Glioma

Glioma is the most common tumor of nervous system. With the development of modern medicine and treatment advances, diagnosis and treatment of glioma had been greatly improved, but its prognosis had not been improved significantly. So the molecular mechanism of the development of glioma and the new breakthroughs in medical research remained a current hot spot.Isocitrate dehydrogenase(IDH1) was one of the key enzymes in the citric acid cycle, and its'encoding gene mutations frequently in glioma. Further studies showed that IDHl mutations decreased its downstream products of a-ketoglutarate (a-KG), thus activated the HIF signaling pathway and promoted glioma formation.This issue analysised the relevance and the possible mechanism of IDHl mutation and stem cell-related genes expression of OCT4 and CD133 in 24 cases of primary and corresponding recurrent glioma tumor samples, in order to further understand the carcinogenic mechanism of IDHl mutation in gliomas and to provide new ideas and experiments for glioma stem cells research. The results showed that: IDH1 mutations have significant correlation with increased expression of OCT4 and CD133 in primary glioma; IDHl mutations have no significant correlation with increased expression of OCT4 and CD133 in glioma recurrence process. Then we detected IDH1, OCT4, CD133 promoter methylation by BSP cloning sequencing and analysised the relation of DNA methylation level and gene expression. The results showed:DNA methylation can regulate the gene expression of OCT4 and CD133 in primary gliomas; The promoter DNA methylation level of OCT4 and CD133 declined in recurrent glioma and it may be one of the main reasons of glioma recurrence; there was no obvious DNA methylation of IDH1 promoter region in gliomas.Taken together, our studies implicate that IDH1 mutations can promote stem cell-related gene expression in primary human glioma, and DNA methylation also play an important role in human glioma occurrence and recurrence. And our studies contribute to understand the pathogenesis of glioma and provided some experimental basis for new direction to explore the clinical treatment of glioma.