From the National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
J Neuropathol Exp Neurol. 2022 Aug 16;81(9):707-716. doi: 10.1093/jnen/nlac059.
Isocitrate dehydrogenase (IDH) mutant gliomas are associated with a better prognosis in comparison to adult IDH wild-type glioma and glioma-CpG island methylator phenotypes. Although OLIG2 is mainly expressed in oligodendrocytes in normal adult brain, it is expressed in both astrocytomas and oligodendrogliomas. Utilizing the clinical, DNA methylation, and RNA-sequencing data from the Cancer Genome Atlas (TCGA) for lower-grade glioma and glioblastoma cohorts, we explored the association between IDH mutation status and OLIG2 expression on transcription, DNA methylation, and gene target levels. Compared to IDH wild-type gliomas, IDH mutant gliomas showed consistently higher expression of OLIG2 transcripts. OLIG2 overexpression is a good surrogate marker for IDH mutation with an AUC of 0.90. At the DNA methylation level, IDH-mutant gliomas showed hyper- and hypomethylation foci upstream of the OLIG2 transcription start site. Underexpressed OLIG2 target genes in IDH mutant glioma were enriched in cell cycle-related pathways. Thus, the differential expression of OLIG2 between IDH mutant and wild-type gliomas reflects involvement in multiple pathways in tumorigenesis.
异柠檬酸脱氢酶（IDH）突变型胶质瘤与成人 IDH 野生型胶质瘤和胶质瘤-CpG 岛甲基化表型相比，预后更好。虽然 OLIG2 主要在正常成人脑中的少突胶质细胞中表达，但它也在星形细胞瘤和少突胶质细胞瘤中表达。利用癌症基因组图谱（TCGA）的临床、DNA 甲基化和 RNA 测序数据，我们探讨了 IDH 突变状态与转录、DNA 甲基化和基因靶点水平上 OLIG2 表达之间的关联。与 IDH 野生型胶质瘤相比，IDH 突变型胶质瘤的 OLIG2 转录本表达水平始终较高。OLIG2 的过表达是 IDH 突变的良好替代标志物，AUC 为 0.90。在 DNA 甲基化水平上，IDH 突变型胶质瘤在 OLIG2 转录起始位点上游表现出超甲基化和低甲基化焦点。IDH 突变型胶质瘤中表达下调的 OLIG2 靶基因富集在细胞周期相关通路中。因此，IDH 突变型和野生型胶质瘤中 OLIG2 的差异表达反映了其在肿瘤发生的多个途径中的参与。
