Abstract：
Glioblastoma, IDH-wild type, the most common malignant primary central nervous system tumor, represents a formidable challenge in clinical management due to its poor prognosis and limited therapeutic responses. With an evolving understanding of its underlying biology, there is an urgent need to identify prognostic molecular groups that can be subject to targeted therapy. This study established a cohort of 124 sequential glioblastomas from a tertiary hospital and aimed to find correlations between molecular features and survival outcomes. Comprehensive molecular characterization of the cohort revealed prevalent alterations as previously described, such as TERT promoter mutations and involvement of the PI3K-Akt-mTOR, CK4/6-CDKN2A/B-RB1, and p14ARF-MDM2-MDM4-p53 pathways. MGMT promoter methylation is a significant predictor of improved overall survival, aligned with previous data. Conversely, age showed a marginal association with higher mortality. Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.
摘要：
胶质母细胞瘤,IDH-野生型,最常见的原发性恶性中枢神经系统肿瘤，由于其预后不良和治疗反应有限，在临床管理中面临巨大挑战。随着对其潜在生物学的不断发展的理解，迫切需要确定可接受靶向治疗的预后分子群.这项研究建立了来自三级医院的124例连续胶质母细胞瘤的队列，旨在发现分子特征与生存结果之间的相关性。队列的综合分子特征揭示了如前所述的普遍改变，如TERT启动子突变和PI3K-Akt-mTOR的参与，CK4/6-CDKN2A/B-RB1和p14ARF-MDM2-MDM4-p53通路。MGMT启动子甲基化是改善总体生存率的重要预测因子。与以前的数据对齐。相反，年龄与较高的死亡率呈边缘相关.多因素分析解释MGMT启动子甲基化和年龄的影响,与其他出版的系列相比，该队列显示，携带PTEN突变的肿瘤的生存率提高，大多数其他分子改变没有观察到差异，包括EGFR扩增,RB1损失，或EGFR扩增和缺失/外显子跳跃（EGFRvIII）的共存。尽管样本量有限，这项研究为胶质母细胞瘤的分子景观提供了数据，促使进一步调查在更大的队列中更仔细地检查这些发现。
