DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets
Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been...
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/4/1342 |
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| author | Ahmad Ozair Vivek Bhat Reid S. Alisch Atulya A. Khosla Rupesh R. Kotecha Yazmin Odia Michael W. McDermott Manmeet S. Ahluwalia |
| author_facet | Ahmad Ozair Vivek Bhat Reid S. Alisch Atulya A. Khosla Rupesh R. Kotecha Yazmin Odia Michael W. McDermott Manmeet S. Ahluwalia |
| author_sort | Ahmad Ozair |
| collection | DOAJ |
| description | Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility. |
| first_indexed | 2024-03-11T09:02:03Z |
| format | Article |
| id | doaj.art-7d2b3f7df52046799e5c489bc2706d1b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:02:03Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7d2b3f7df52046799e5c489bc2706d1b2023-11-16T19:39:40ZengMDPI AGCancers2072-66942023-02-01154134210.3390/cancers15041342DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical TargetsAhmad Ozair0Vivek Bhat1Reid S. Alisch2Atulya A. Khosla3Rupesh R. Kotecha4Yazmin Odia5Michael W. McDermott6Manmeet S. Ahluwalia7Miami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USASt. John’s Medical College, Bangalore 560034, IndiaDepartment of Neurosurgery, University of Wisconsin-Madison, Madison, WI 53792, USAMiami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USAMiami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USAMiami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USAHerbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USAMiami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USAGliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility.https://www.mdpi.com/2072-6694/15/4/1342methylationmethylomicsG-CIMPMGMTDNMTATRX |
| spellingShingle | Ahmad Ozair Vivek Bhat Reid S. Alisch Atulya A. Khosla Rupesh R. Kotecha Yazmin Odia Michael W. McDermott Manmeet S. Ahluwalia DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets Cancers methylation methylomics G-CIMP MGMT DNMT ATRX |
| title | DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets |
| title_full | DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets |
| title_fullStr | DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets |
| title_full_unstemmed | DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets |
| title_short | DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets |
| title_sort | dna methylation and histone modification in low grade gliomas current understanding and potential clinical targets |
| topic | methylation methylomics G-CIMP MGMT DNMT ATRX |
| url | https://www.mdpi.com/2072-6694/15/4/1342 |
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