Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.
Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.
复制标题
DOI：
10.18632/oncotarget.1765
复制
发表时间：
2014-03-30
期刊：
影响因子：
--
通讯作者：
Bigner DD
中科院分区：
文献类型：
--
作者：
Killela PJ;Pirozzi CJ;Healy P;Reitman ZJ;Lipp E;Rasheed BA;Yang R;Diplas BH;Wang Z;Greer PK;Zhu H;Wang CY;Carpenter AB;Friedman H;Friedman AH;Keir ST;He J;He Y;McLendon RE;Herndon JE 2nd;Yan H;Bigner DD
异柠檬酸脱氢酶1和2 （IDH1和IDH2）和端粒酶逆转录酶启动子（TERT）的频繁突变代表了胶质瘤基因组学的两个重大发现。了解这两种突变在胶质瘤亚型中共同发生或单独发生的程度，为指导胶质瘤的分类和预后提供了独特的机会。我们分析了473例成年胶质瘤患者的总生存期（OS）与IDH1/2和TERT启动子突变之间的关系。我们假设并证明能够区分几种类型胶质瘤的遗传特征可以建立，提供临床相关信息，可以作为组织病理学诊断的辅助手段。我们发现TERT启动子突变发生在74.2%的胶质母细胞瘤（GBM）中，但发生在少数II-III级星形细胞瘤中（18.2%）。相比之下，在78.4%的II-III级星形细胞瘤中观察到IDH1/2突变，但在原发性GBM中并不常见。在少突胶质细胞瘤中，TERT启动子和IDH1/2突变在79%的病例中同时发生。III-IV级胶质瘤仅表现TERT启动子突变的患者主要有原发性GBMs，中位OS差（11.5个月）。III-IV级胶质瘤仅表现IDH1/2突变的患者主要表现为星形细胞形态，中位生存期为57个月，而肿瘤同时表现TERT启动子和IDH1/2突变的患者主要表现为少突胶质形态，中位生存期为125个月。根据胶质瘤的遗传特征分析胶质瘤，可以将这些患者分层为不同的队列，具有独特的预后和生存率。
Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.