DNA hydroxymethylation in high-grade gliomas.

Background and Study Aims Since the new WHO classification of nervous system tumors (2016 revised 4th edition) has been released, gliomas are classified depending on molecular and genetic markers in connection with histopathology, instead of histopathology itself as it was in the previous classification. Over the last years, epigenetic analysis has taken on increased importance in the diagnosis and treatment of different cancers. Multiple studies confirmed that DNA methylation and hydroxymethylation play an important role in the regulation of gene expression during carcinogenesis. In this review, we aim to present the current state of knowledge on DNA hydroxymethylation in human high-grade gliomas (WHO grade III and IV). Results The correlation of DNA hydroxymethylation and survival in glioblastoma patients was evaluated by different studies. The majority of them showed that the expression of 5-hydroxymethylcytosine (5-hmC) and Ten-eleven translocation (TET) enzymes were significantly reduced, sometimes almost undetectable in high-grade gliomas in comparison with the control brain. A decreased level of 5-hmC was associated with poor survival in patients, but high expression of the TET3 enzyme was related to a better prognosis for GBM patients. This points to the relevance of DNA hydroxymethylation in molecular diagnostics of human gliomas, including survival estimation or differentiating patients in terms of response to the treatment. Conclusion Future studies may shed some more light on this epigenetic mechanism involved in the pathogenesis of human high-grade gliomas and help to develop new targeted therapies.