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.

胶质瘤表现出表观遗传失调，例如IDH1突变肿瘤中的胶质瘤 CpG 岛甲基化表型 (G-CIMP)。5-羟甲基胞嘧啶 (5hmC) 与胶质瘤发病机制有关；然而，它在IDH1突变型胶质瘤中的作用尚不完全清楚。为了进一步表征IDH1突变型胶质瘤中的 5hmC，我们使用定量基因座特异性方法检查了IDH1突变型和野生型高级别胶质瘤 (HGG) 中的 5hmC。显示出高 5hmC 丰度和差异羟甲基化区域 (DHMR) 的区域富含与胶质瘤发病机制有关的增强子。在这些区域中，IDH1与野生型相比，突变型肿瘤具有更大的 5hmC。5hmC 有助于 G-CIMP 基因的整体甲基化状态。5hmC 靶向基因体区域与增加的基因表达显着相关。特别是，对于IDH1突变组中高表达的基因，确定了增加的 5hmC 和增加的基因表达之间的强相关性。总体而言，5hmC 靶向调控区域并与过表达基因相关的基因座特异性增益表明 5hmC 在IDH1突变 HGG 中的重要作用。