Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
Department of Neurosurgery, Singapore General Hospital, Outram Rd, Singapore, 169608, Singapore.
BMC Cancer. 2020 Jan 31;20(1):79. doi: 10.1186/s12885-020-6536-x.
Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population.
Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test.
181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006).
The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.
神经胶质瘤由一组异质性肿瘤组成。本研究旨在报告在一个种族多样化的人群中高级别神经胶质瘤中 O-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）启动子甲基化、1p19q 共缺失、异柠檬酸脱氢酶（IDH）基因突变和 X 连锁α-地中海贫血/智力低下综合征（ATRX）失活突变的发生率。
获取了我院 2013 年 1 月至 2017 年 3 月期间接受高级别神经胶质瘤手术的患者的病历。记录患者的年龄、性别、种族、卡氏功能状态评分（KPS）、日常生活活动能力（ADL）、肿瘤位置和生物标志物状态。采用卡方检验和曼-惠特尼 U 检验、Kaplan-Meier 估计和对数秩检验进行数据分析。
选择了 181 例患者（56 例为 3 级神经胶质瘤，125 例为 4 级神经胶质瘤）。在 3 级组中，55%的患者 MGMT 启动子甲基化，41%的患者 1p19q 共缺失，35%的患者 IDH1 突变，无一例 ATRX 缺失。在 4 级组中，30%的患者 MGMT 启动子甲基化，2%的患者 1p19q 共缺失，15%的患者 IDH1 突变，8%的患者 ATRX 缺失。在校正年龄、手术和术前 ADL 状态的影响后，仅在 3 级（p=0.024）和 4 级患者中发现 MGMT 启动子甲基化与总生存时间显著相关（p=0.006）。
MGMT 启动子甲基化和 IDH1 突变的发生率与全球报道的比率相当，但 1p19q 共缺失和 ATRX 缺失的发生率似乎在我们的队列中较低。MGMT 启动子甲基化与我们队列中的总生存时间增加相关，可能是一个有利的预后因素。
