Book. 2017 09 27

Authors: De Vleeschouwer S

Aberrant DNA methylation is a common event in the genesis and progression of tumors. The application of next-generation sequencing enables the identification and mapping of DNA methylation and its derivatives, 5fC and 5hmC, to base-pair resolution. This chapter describes nine novel hypermethylation genes and six hypomethylation genes, identified by constructing a DNA methylation profile, in glioblastoma. Abnormal promoter methylation and histone modifications were associated with differential expression of miRNAs in glioblastoma: miR-185 reversed global DNA methylation and the methylation level of the hypermethylation genes by targeting DNMT; and miR-101 regulated histone methylation of hypomethylation genes by targeting EED, EZH2, and DNMT3A. The long noncoding RNA CASC2c directly bound to miR-101 via microRNA response elements, and there was a reciprocal repression between CASC2c and miR-101. Despite being competitors they both led to the overexpression of their target hypomethylation genes CPEB1, PRDM16, and LMO3. Taken together, glioblastoma is a complicated pathological process with deregulated methylation and histone modifications. Focal differentially methylated region and differentially methylated site studies will be helpful for the identification of regulatory elements of transcription. Studies of intragenic and distant intergenic alterations in DNA methylation will help elucidate the nature of epigenetic deregulation in glioblastoma.

PMID: 29251856

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