Department of Biology, San Francisco State University, San Francisco, CA 94132, USA.
Int J Mol Sci. 2021 Jan 20;22(3):1020. doi: 10.3390/ijms22031020.
DNA methylation is an epigenetic change to the genome that impacts gene activities without modification to the DNA sequence. Alteration in the methylation pattern is a naturally occurring event throughout the human life cycle which may result in the development of diseases such as cancer. In this study, we analyzed methylation data from The Cancer Genome Atlas, under the Lower-Grade Glioma (LGG) and Glioblastoma Multiforme (GBM) projects, to identify methylation markers that exhibit unique changes in DNA methylation pattern along with tumor grade progression, to predict patient survival. We found ten glioma grade-associated Cytosine-phosphate-Guanine (CpG) sites that targeted four genes (, and ) and the methylation pattern is strongly associated with glioma specific molecular alterations, primarily isocitrate dehydrogenase (IDH) mutation and chromosome 1p/19q codeletion. The ten CpG sites collectively distinguished a cohort of diffuse glioma patients with remarkably poor survival probability. Our study highlights genes ( and ) that were not previously associated with gliomas to have contributed to the poorer patient outcome. These CpG sites can aid glioma tumor progression monitoring and serve as prognostic markers to identify patients diagnosed with less aggressive and malignant gliomas that exhibit similar survival probability to GBM patients.
DNA 甲基化是基因组的一种表观遗传改变，它影响基因活性，而不会改变 DNA 序列。甲基化模式的改变是人类生命周期中自然发生的事件，可能导致癌症等疾病的发展。在这项研究中，我们分析了癌症基因组图谱中的甲基化数据，这些数据来自低级别神经胶质瘤（LGG）和多形性胶质母细胞瘤（GBM）项目，以鉴定在肿瘤分级进展过程中表现出独特 DNA 甲基化模式变化的甲基化标记物，从而预测患者的生存情况。我们发现了十个与神经胶质瘤分级相关的胞嘧啶-磷酸-鸟嘌呤（CpG）位点，这些位点靶向四个基因（、和），并且甲基化模式与神经胶质瘤特异性分子改变密切相关，主要是异柠檬酸脱氢酶（IDH）突变和染色体 1p/19q 缺失。这十个 CpG 位点共同区分了弥漫性神经胶质瘤患者的亚群，这些患者的生存概率明显较差。我们的研究强调了以前与神经胶质瘤无关的基因（和），这些基因导致了患者预后较差。这些 CpG 位点可以帮助监测神经胶质瘤肿瘤的进展，并作为预后标志物，以识别出具有相似生存概率的侵袭性和恶性较低的神经胶质瘤患者，这些患者与 GBM 患者相似。
