Incekara Fatih, van der Voort Sebastian R, Dubbink Hendrikus J, Atmodimedjo Peggy N, Nandoe Tewarie Rishi, Lycklama Geert, Vincent Arnaud J P E, Kros Johan M, Klein Stefan, van den Bent Martin, Smits Marion
Department of Neurosurgery, Brain Tumor Center, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands.
Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, Netherlands.
Front Oncol. 2020 May 12;10:596. doi: 10.3389/fonc.2020.00596. eCollection 2020.
O methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. without MGMT promoter methylation, possibly caused by molecular heterogeneity in glioblastoma populations. We initiated this study to re-evaluate the topographical distribution of glioblastoma with vs. without MGMT promoter methylation in light of the updated WHO 2016 classification. Preoperative T2-weighted/FLAIR and postcontrast T1-weighted MRI scans of patients aged 18 year or older with IDH wildtype glioblastoma were collected. Tumors were semi-automatically segmented, and the topographical distribution between glioblastoma with vs. without MGMT promoter methylation was visualized using frequency heatmaps. Then, voxel-wise differences were analyzed using permutation testing with Threshold Free Cluster Enhancement. Four hundred thirty-six IDH wildtype glioblastoma patients were included; 211 with and 225 without MGMT promoter methylation. Visual examination suggested that when compared with MGMT unmethylated glioblastoma, MGMT methylated glioblastoma were more frequently located near bifrontal and left occipital periventricular area and less frequently near the right occipital periventricular area. Statistical analyses, however, showed no significant difference in topographical distribution between MGMT methylated vs. MGMT unmethylated glioblastoma. This study re-evaluated the topographical distribution of MGMT promoter methylation in 436 newly diagnosed IDH wildtype glioblastoma, which is the largest homogenous IDH wildtype glioblastoma population to date. There was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma.
O-甲基鸟嘌呤-甲基转移酶(MGMT)启动子甲基化和异柠檬酸脱氢酶(IDH)突变状态是胶质母细胞瘤患者重要的预后因素。关于有或无MGMT启动子甲基化的胶质母细胞瘤的不同地形分布,存在相互矛盾的报道,这可能是由胶质母细胞瘤群体中的分子异质性导致的。我们开展这项研究,根据世界卫生组织2016年更新的分类重新评估有或无MGMT启动子甲基化的胶质母细胞瘤的地形分布。收集了年龄在18岁及以上的IDH野生型胶质母细胞瘤患者术前的T2加权/液体衰减反转恢复序列(FLAIR)和增强后T1加权磁共振成像(MRI)扫描图像。对肿瘤进行半自动分割,并使用频率热图可视化有或无MGMT启动子甲基化的胶质母细胞瘤之间的地形分布。然后,使用无阈值聚类增强的置换检验分析体素水平的差异。纳入了436例IDH野生型胶质母细胞瘤患者;其中211例有MGMT启动子甲基化,225例无MGMT启动子甲基化。视觉检查表明,与MGMT未甲基化的胶质母细胞瘤相比,MGMT甲基化的胶质母细胞瘤更常位于双额叶和左侧枕叶脑室周围区域,而较少位于右侧枕叶脑室周围区域。然而,统计分析显示,MGMT甲基化与未甲基化的胶质母细胞瘤在地形分布上没有显著差异。本研究重新评估了436例新诊断的IDH野生型胶质母细胞瘤中MGMT启动子甲基化的地形分布,这是迄今为止最大的同质IDH野生型胶质母细胞瘤群体。MGMT甲基化与未甲基化的IDH野生型胶质母细胞瘤在解剖定位上没有统计学显著差异。