Higa Nayuta, Akahane Toshiaki, Yokoyama Seiya, Makino Ryutaro, Yonezawa Hajime, Uchida Hiroyuki, Takajo Tomoko, Kirishima Mari, Hamada Taiji, Noguchi Naoki, Otsuji Ryosuke, Kuga Daisuke, Nagasaka Shohei, Yamahata Hitoshi, Yamamoto Junkoh, Yoshimoto Koji, Tanimoto Akihide, Hanaya Ryosuke
Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Neurooncol Adv. 2023 Jun 28;5(1):vdad078. doi: 10.1093/noajnl/vdad078. eCollection 2023 Jan-Dec.
promoter () mutations are a biological marker of glioblastoma; however, the prognostic significance of mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase ( and -type glioblastomas.
Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type .
mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were -wild-type. Among the -wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without loss and/or mutation. Patients with -wild-type glioblastomas with loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without loss and/or mutation. We divided the patients with -wild-type into 3 clusters using unsupervised hierarchical clustering: Good ( and alterations; lack of homozygous deletion and alterations), intermediate ( alterations, homozygous deletion, lack of and alterations), and poor ( and alterations, homozygous deletion, and lack of alterations) outcomes. Kaplan-Meier survival analysis indicated that these clusters significantly correlated with the overall survival of -wild-type glioblastoma patients.
Here, we report that loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with - and -wild-type glioblastomas. The combination of 4 genes, , , , and , is important for the molecular classification and individual prognosis of patients with - and -wild-type glioblastomas.
启动子（）突变是胶质母细胞瘤的一种生物学标志物；然而，突变状态的预后意义存在争议。我们通过回顾性分析异柠檬酸脱氢酶（和型胶质母细胞瘤患者的预后情况来评估这种影响。
使用定制的二代测序技术，我们分析了208例携带野生型的胶质母细胞瘤样本。
在143个样本（68.8%）中检测到突变。其余65个（31.2%）为野生型。在野生型胶质母细胞瘤样本中，我们观察到有无缺失和/或突变的患者在无进展生存期（分别为18.6个月和11.4个月）和总生存期（分别为未达到和15.7个月）方面存在显著差异。有缺失和/或突变的野生型胶质母细胞瘤患者比无缺失和/或突变的患者更年轻，卡氏功能状态评分更高。我们使用无监督层次聚类将野生型患者分为3个簇：良好（和改变；无纯合缺失和改变）、中等（改变、纯合缺失、无和改变）和不良（和改变、纯合缺失、无改变）预后。Kaplan-Meier生存分析表明，这些簇与野生型胶质母细胞瘤患者的总生存期显著相关。
在此，我们报告缺失和/或突变是预测野生型和野生型胶质母细胞瘤患者良好预后最有用的标志物。、、、和这4个基因的组合对于野生型和野生型胶质母细胞瘤患者的分子分类和个体预后很重要。
