Epigenetics and its Reflections in Gliomas

Dilara AKCORA YILDIZa

aBurdur Mehmet Akif Ersoy University Faculty of Science and Letters, Department of Biology, Burdur, Türkiye

Akcora Yıldız D. Epigenetics and its reflec- tions in gliomas. In: Uğur HÇ, Bayatlı E, eds. Glial Tumours: Expectations from Today-Pro- mises of the Future. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.10-7.

ABSTRACT

Gliomas represent the most frequently occurring malignant primary brain tumors in adults, presenting a significant clinical challenge due to their high recurrence rates and related mortality. Al- though there have been improvements in treatment approaches, such as surgery, chemotherapy, and ra- diotherapy, gliomas remain difficult to cure. This highlights the need for more effective and personalized approaches to therapy. In the past two decades, large-scale multi-omic studies have provided insights into the molecular complexities of gliomas, highlighting distinct patterns of epigenetic dysregulation that dis- tinguish various subtypes and are linked to differences in patient outcomes. Epigenetic dysregulation, a key feature of glioma biology, refers to heritable but reversible modifications in gene expression that take place without changing the DNA sequence. These modifications are regulated by mechanisms including methylation of DNA, alterations to histone proteins, chromatin restructuring, regulation of non-coding RNAs, and RNA-related epigenetics. These mechanisms operate in a synchronized manner to precisely control gene expression at specific times and locations. Understanding the role of these intricate epigenetic systems is crucial, as they play a significant role in the initiation, progression, and treatment resistance of gliomas. One significant epigenetic feature is the Glioma CpG Island Methylator Phenotype (G-CIMP), which serves as a potential diagnostic tool for distinguishing glioma subgroups and predicting patient out- comes. The other most well-known example of epigenetic regulation in gliomas is the methylation of the MGMT promoter, which predicts a better response to alkylating agents like temozolomide. This part aims to provide a better understanding of the crucial epigenetic processes driving glioma biology, as these mechanisms are essential for developing new therapies. Additionally, it covers epigenetic treatments, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, which are being investigated clin- ically as possible therapies to get past resistance and enhance glioma patient outcomes.

Keywords: Glioma; IDH mutation; epigenetics; DNA methylation; histone modifications; MGMT; epigenetic drugs

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