5-Hydroxymethylcytosine preferentially targets genes upregulated in isocitrate dehydrogenase 1 mutant high-grade glioma
| Autor: | Yasin Mamatjan, Michael D. Taylor, Harshika Jain, Abulizi Maimaitiming, Wioletta Glowacka, Hamza Farooq, Paul Kongkham, Makiko Okura, Kenneth Aldape, Romina Nejad |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine IDH1 Mutant Biology Pathology and Forensic Medicine Cohort Studies 03 medical and health sciences Cellular and Molecular Neuroscience Glioma Gene expression medicine Humans RNA Messenger Epigenetics neoplasms Gene Aged Brain Neoplasms Wild type DNA Methylation Middle Aged medicine.disease Isocitrate Dehydrogenase Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology 5-Methylcytosine Cancer research Female Body region Neurology (clinical) Neoplasm Grading |
| Zdroj: | Acta Neuropathologica. 135:617-634 |
| ISSN: | 1432-0533 0001-6322 |
| Popis: | Gliomas demonstrate epigenetic dysregulation exemplified by the Glioma CpG Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-Hydroxymethylcytosine (5hmC) is implicated in glioma pathogenesis; however, its role in IDH1 mutant gliomas is incompletely understood. To characterize 5hmC in IDH1 mutant gliomas further, we examine 5hmC in a cohort of IDH1 mutant and wild-type high-grade gliomas (HGG) using a quantitative locus-specific approach. Regions demonstrating high 5hmC abundance and differentially hydroxymethylated regions (DHMR) enrich for enhancers implicated in glioma pathogenesis. Among these regions, IDH1 mutant tumors possess greater 5hmC compared to wild type. 5hmC contributes to overall methylation status of G-CIMP genes. 5hmC targeting gene body regions correlates significantly with increased gene expression. In particular, a strong correlation between increased 5hmC and increased gene expression is identified for genes highly expressed in the IDH1 mutant cohort. Overall, locus-specific gain of 5hmC targeting regulatory regions and associated with overexpressed genes suggests a significant role for 5hmC in IDH1 mutant HGG. |
| Databáze: | OpenAIRE |
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