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Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4) have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ), and even low grade gliomas (LGGs, WHO grade 2) eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the  O   6 -methylguanine-DNA methyltransferase ( MGMT ) that is the main determinant of resistance to TMZ, recent studies suggested that  MGMT  promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP) in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that  MGMT  promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of  MGMT  promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1)  IDH1/2  mutation is closely correlated with  MGMT  promoter methylation and  1p/19q  codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to  MGMT  promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to  MGMT  promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.

The Global DNA Methylation Surrogate LINE-1 Methylation Is Correlated with MGMT Promoter Methylation and Is a Better Prognostic Factor for Glioma