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Open AccessArticle

MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System

1
Institute of Neuropathology, University Hospital Essen, D-45147 Essen, Germany
2
Institute of Pathology, University Hospital Essen, D-45147 Essen, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Javier Conde Aranda and Morena Scotece
Int. J. Mol. Sci. 2021, 22(8), 3845; https://doi.org/10.3390/ijms22083845
Received: 7 March 2021 / Revised: 5 April 2021 / Accepted: 5 April 2021 / Published: 8 April 2021
Quantifying O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation plays an essential role in assessing the potential efficacy of alkylating agents in the chemotherapy of malignant gliomas. MGMT promoter methylation is considered to be a characteristic of subgroups of certain malignancies but has also been described in various peripheral inflammatory diseases. However, MGMT promoter methylation levels have not yet been investigated in non-neoplastic brain diseases. This study demonstrates for the first time that one can indeed detect slightly enhanced MGMT promoter methylation in individual cases of inflammatory demyelinating CNS diseases such as multiple sclerosis and progressive multifocal leucencephalopathy (PML), as well as in other demyelinating diseases such as central pontine and exptrapontine myelinolysis, and diseases with myelin damage such as Wallerian degeneration. In this context, we identified a reduction in the expression of the demethylase TET1 as a possible cause for the enhanced MGMT promoter methylation. Hence, we show for the first time that MGMT hypermethylation occurs in chronic diseases that are not strictly associated to distinct pathogens, oncogenic viruses or neoplasms but that lead to damage of the myelin sheath in various ways. While this gives new insights into epigenetic and pathophysiological processes involved in de- and remyelination, which might offer new therapeutic opportunities for demyelinating diseases in the future, it also reduces the specificity of MGMT hypermethylation as a tumor biomarker. View Full-Text
Keywords: DNA-methylation; MGMT promoter methylation; multiple sclerosis; progressive multifocal leucencephalopathy (PML); central pontine and exptrapontine myelinolysis; Wallerian degeneration DNA-methylation; MGMT promoter methylation; multiple sclerosis; progressive multifocal leucencephalopathy (PML); central pontine and exptrapontine myelinolysis; Wallerian degeneration
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MDPI and ACS Style

Teuber-Hanselmann, S.; Worm, K.; Macha, N.; Junker, A. MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System. Int. J. Mol. Sci. 2021, 22, 3845. https://doi.org/10.3390/ijms22083845

AMA Style

Teuber-Hanselmann S, Worm K, Macha N, Junker A. MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System. International Journal of Molecular Sciences. 2021; 22(8):3845. https://doi.org/10.3390/ijms22083845

Chicago/Turabian Style

Teuber-Hanselmann, Sarah; Worm, Karl; Macha, Nicole; Junker, Andreas. 2021. "MGMT-Methylation in Non-Neoplastic Diseases of the Central Nervous System" Int. J. Mol. Sci. 22, no. 8: 3845. https://doi.org/10.3390/ijms22083845

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