Study On Methylation, Mutation And Expression Of TERT Gene In Patients With Glioma

The telomerase reverse transcriptase gene (TERT) encodes the reverse transcriptase component of the telomerase complex, and plays an essential role in telomere stabilization and cell immortalization. TERT activation was tightly controlled in several human cancers. However, the regulation mechanism for TERT activation in gliomas is still largely unknown. Previous studies have shown that C228T and C250T mutation in the promoter region of TERT result in upregulation of TERT expression. And the DNA methylation of TERT promoter will also influence the TERT expression in adult gliomas.A total of 77 Chinese adults gliomas were evaluated in this study. TERT C228T and C250T mutations were assessed by direct Sanger sequencing and methylation of an identified region of the TERT promoter and IDH1 mutation were analyzed by pyrosequencing. TERT mRNA expression levels were determined by quantitative RT-PCR.TERT mRNA expression was significantly elevated in TERT promoter mutation patients (p= 0.005). TERT promoter methylation level was significant differences between different grades of gliomas. The methylation level was high in high grade gliomas. The association between TERT promoter methylation and mRNA expression was not statistical significant. However, TERT mRNA expression level was inversely correlated with TERT promoter methylation in IDH1 mutated subgroup patients. Additionally, the TERT promoter hypermethylation was significantly associated with IDH1 mutation (p= 0.023); TERT mutation was also found most frequently occured in grade IV gliomas (42.9% of 9/21), the most common and malignant human brain tumor.Our data indicated that TERT mutation, IDH1 mutation and TERT promoter methylation work together work together to regulate TERT mRNA expression in adult gliomas. And TERT is a potentially accessible biomarker for gliomas.