Stapińska-Syniec Angelika, Grabiec Marta, Rylski Marcin, Acewicz Albert, Sobstyl Michał
Department of Neurosurgery, Instytut Psychiatrii i Neurologii, Warsaw, Poland.
Department of Clinical Cytology, Centrum Medyczne Ksztalcenia Podyplomowego, Warszawa, Poland.
J Neurol Surg A Cent Eur Neurosurg. 2022 Nov;83(6):568-572. doi: 10.1055/a-1713-7699. Epub 2021 Dec 6.
Since the new World Health Organization (WHO) classification of nervous system tumors (2016, revised, 4th edition) has been released, gliomas are classified depending on molecular and genetic markers in connection with histopathology, instead of histopathology itself as it was in the previous classification. Over the last years, epigenetic analysis has taken on increased importance in the diagnosis and treatment of different cancers. Multiple studies confirmed that deoxyribonucleic acid (DNA) methylation and hydroxymethylation play an important role in the regulation of gene expression during carcinogenesis.
In this review, we aim to present the current state of knowledge on DNA hydroxymethylation in human high-grade gliomas (WHO grades III and IV).
The correlation between DNA hydroxymethylation and survival in glioblastoma multiforme (GBM) patients was evaluated by different studies. The majority of them showed that the expression of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation (TET) enzymes were significantly reduced, sometimes almost undetectable in high-grade gliomas in comparison with the normal brain. A decreased level of 5-hmC was associated with poor survival in patients, but high expression of the TET3 enzyme was related to a better prognosis for GBM patients. This points to the relevance of DNA hydroxymethylation in molecular diagnostics of human gliomas, including survival estimation or differentiating patients in terms of response to the treatment.
Future studies may shed some more light on this epigenetic mechanism involved in the pathogenesis of human high-grade gliomas and help develop new targeted therapies.
自世界卫生组织（WHO）新版神经系统肿瘤分类（2016年修订第4版）发布以来，胶质瘤是根据与组织病理学相关的分子和基因标志物进行分类的，而非像之前分类那样仅依据组织病理学本身。在过去几年中，表观遗传学分析在不同癌症的诊断和治疗中变得愈发重要。多项研究证实，脱氧核糖核酸（DNA）甲基化和羟甲基化在致癌过程中基因表达的调控中发挥着重要作用。
在本综述中，我们旨在阐述人类高级别胶质瘤（WHO III级和IV级）中DNA羟甲基化的当前知识状态。
不同研究评估了DNA羟甲基化与多形性胶质母细胞瘤（GBM）患者生存之间的相关性。大多数研究表明，与正常脑组织相比，5-羟甲基胞嘧啶（5-hmC）和十-十一易位（TET）酶的表达在高级别胶质瘤中显著降低，有时几乎检测不到。5-hmC水平降低与患者生存不良相关，但TET3酶的高表达与GBM患者的较好预后相关。这表明DNA羟甲基化在人类胶质瘤的分子诊断中具有相关性，包括生存评估或区分患者对治疗的反应。
未来的研究可能会进一步阐明这种参与人类高级别胶质瘤发病机制的表观遗传机制，并有助于开发新的靶向治疗方法。
