Brągiel-Pieczonka Aneta, Lipka Gabriela, Stapińska-Syniec Angelika, Czyżewski Michał, Żybura-Broda Katarzyna, Sobstyl Michał, Rylski Marcin, Grabiec Marta
Department of Clinical Cytology, Centre of Postgraduate Medical Education, Warsaw, Poland.
Department of Neurosurgery, Institute of Psychiatry and Neurology, Warsaw, Poland.
Front Oncol. 2022 Apr 14;12:621460. doi: 10.3389/fonc.2022.621460. eCollection 2022.
Gliomas are the most common primary malignant intracranial brain tumors. Their proliferative and invasive behavior is controlled by various epigenetic mechanisms. 5-hydroxymethylcytosine (5-hmC) is one of the epigenetic DNA modifications that employs ten-eleven translocation (TET) enzymes to its oxidation. Previous studies demonstrated altered expression of 5-hmC across gliomagenesis. However, its contribution to the initiation and progression of human gliomas still remains unknown. To characterize the expression profiles of 5-hmC and TET in human glioma samples we used the EpiJET 5-hmC and 5-mC Analysis Kit, quantitative real-time PCR, and Western blot analysis. A continuous decline of 5-hmC levels was observed in solid tissue across glioma grades. However, in glioblastoma (GBM), we documented uncommon heterogeneity in 5-hmC expression. Further analysis showed that the levels of TET proteins, but not their transcripts, may influence the 5-hmC abundance in GBM. Early tumor-related biomarkers may also be provided by the study of aberrant DNA hydroxymethylation in the blood of glioma patients. Therefore, we explored the patterns of TET transcripts in plasma samples and we found that their profiles were variously regulated, with significant value for . The results of our study confirmed that DNA hydroxymethylation is an important mechanism involved in the pathogenesis of gliomas, with particular reference to glioblastoma. Heterogeneity of 5-hmC and TET proteins expression across GBM may provide novel insight into define subtype-specific patterns of hydroxymethylome, and thus help to interpret the heterogeneous outcomes of patients with the same disease.
胶质瘤是最常见的原发性恶性颅内脑肿瘤。它们的增殖和侵袭行为受多种表观遗传机制控制。5-羟甲基胞嘧啶（5-hmC）是一种表观遗传DNA修饰，它利用十-十一易位（TET）酶进行氧化。先前的研究表明，在胶质瘤发生过程中5-hmC的表达发生了改变。然而，其对人类胶质瘤起始和进展的作用仍不清楚。为了表征5-hmC和TET在人类胶质瘤样本中的表达谱，我们使用了EpiJET 5-hmC和5-mC分析试剂盒、定量实时PCR和蛋白质免疫印迹分析。在不同级别的胶质瘤实体组织中均观察到5-hmC水平持续下降。然而，在胶质母细胞瘤（GBM）中，我们记录到5-hmC表达存在罕见的异质性。进一步分析表明，TET蛋白的水平而非其转录本可能影响GBM中5-hmC的丰度。对胶质瘤患者血液中异常DNA羟甲基化的研究也可能提供早期肿瘤相关生物标志物。因此，我们探索了血浆样本中TET转录本的模式，发现它们的表达谱受到不同调控，具有显著意义。我们的研究结果证实，DNA羟甲基化是胶质瘤发病机制中的一个重要机制，尤其是在胶质母细胞瘤中。GBM中5-hmC和TET蛋白表达的异质性可能为定义羟甲基化组的亚型特异性模式提供新的见解，从而有助于解释同病患者的异质性结局。
