Sansone Giulio, Lombardi Giuseppe, Maccari Marta, Gaiola Matteo, Pini Lorenzo, Cerretti Giulia, Guerriero Angela, Volpin Francesco, Denaro Luca, Corbetta Maurizio, Salvalaggio Alessandro
Department of Neuroscience, University of Padova, 35121 Padova, Italy.
Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
Brain Commun. 2024 Dec 3;6(6):fcae415. doi: 10.1093/braincomms/fcae415. eCollection 2024.
A large literature assessed the relationships between the O-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and glioblastoma location with inconsistent results. Studies assessing this association using the percentage of methylation are lacking. This cross-sectional study aimed at investigating relationships between glioblastoma topology and MGMT promoter methylation, both as categorical (presence/absence) and continuous (percentage) status. We included patients with diagnosis of isocitrate dehydrogenase wild-type glioblastoma [World Health Organization (WHO) 2021 classification], available pre-surgical MRI, known MGMT promoter methylation status. Quantitative methylation assessment was obtained through pyrosequencing. Several analyses were performed for categorical and continuous variables ( , -tests, ANOVA and Pearson's correlations), investigating relationships between MGMT methylation and glioblastoma location in cortex/white matter/deep grey matter nuclei, lobes, left/right hemispheres and functional grey and white matter network templates. Furthermore, we assessed at the voxel-wise level location differences between (i) methylated and unmethylated glioblastomas and (ii) highly and lowly methylated glioblastomas. Lastly, we investigated the linear relationship between glioblastoma-voxel location and the MGMT methylation percentage. Ninety-three patients were included (66 males; mean age: 62.3 ± 11.3 years), and 42 were MGMT methylated. The mean methylation level was 33.9 ± 18.3%. No differences in glioblastoma volume and location were found between MGMT-methylated and MGMT-unmethylated patients. No specific anatomical regions were associated with MGMT methylation at the voxel-wise level. MGMT methylation percentage positively correlated with cortical localization ( = 0.36, = 0.021) and negatively with deep grey matter nuclei localization ( = -0.35, = 0.025). To summarize, we investigated relationships between MGMT methylation status and glioblastoma location through multiple approaches, including voxel-wise analyses. In conclusion, MGMT promoter methylation percentage positively correlated with cortical glioblastoma location, while no specific anatomical regions were associated with MGMT methylation status.
大量文献评估了O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化状态与胶质母细胞瘤位置之间的关系，但结果不一致。目前缺乏使用甲基化百分比评估这种关联的研究。这项横断面研究旨在调查胶质母细胞瘤拓扑结构与MGMT启动子甲基化之间的关系，包括分类（存在/不存在）和连续（百分比）状态。我们纳入了诊断为异柠檬酸脱氢酶野生型胶质母细胞瘤[世界卫生组织（WHO）2021分类]、有术前MRI且已知MGMT启动子甲基化状态的患者。通过焦磷酸测序进行定量甲基化评估。对分类变量和连续变量进行了多项分析（t检验、方差分析和Pearson相关性分析），研究MGMT甲基化与胶质母细胞瘤在皮质/白质/深部灰质核、脑叶、左右半球以及功能灰质和白质网络模板中的位置之间的关系。此外，我们在体素水平评估了（i）甲基化和未甲基化胶质母细胞瘤之间以及（ii）高甲基化和低甲基化胶质母细胞瘤之间的位置差异。最后，我们研究了胶质母细胞瘤体素位置与MGMT甲基化百分比之间的线性关系。纳入了93例患者（66例男性；平均年龄：62.3±11.3岁），其中42例MGMT甲基化。平均甲基化水平为33.9±18.3%。MGMT甲基化和未甲基化患者之间在胶质母细胞瘤体积和位置上未发现差异。在体素水平上，没有特定的解剖区域与MGMT甲基化相关。MGMT甲基化百分比与皮质定位呈正相关（r = 0.36，P = 0.021），与深部灰质核定位呈负相关（r = -0.35，P = 0.025）。总之，我们通过多种方法，包括体素水平分析，研究了MGMT甲基化状态与胶质母细胞瘤位置之间的关系。总之，MGMT启动子甲基化百分比与皮质胶质母细胞瘤位置呈正相关，而没有特定的解剖区域与MGMT甲基化状态相关。
