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IDH 突变和 MGMT 启动子状态在二级高级别胶质瘤中的预后价值。

The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

机构信息

Department of Neurosurgery, University Hospital Carl Gustav Carus, Dresden University of Technology, Fetscherstrasse 74, 01307, Dresden, Germany.

出版信息

J Neurooncol. 2012 Dec;110(3):325-33. doi: 10.1007/s11060-012-0977-2. Epub 2012 Sep 27.

Abstract

Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

摘要

关于 IDH 突变和 O6-甲基鸟嘌呤-DNA 甲基转移酶基因启动子区在继发性高级别神经胶质瘤(sHGG)中的预后价值的报道很少。我们研究了 99 例 sHGG 患者中 IDH 突变和 MGMT 基因启动子区甲基化的预后价值,并分析了这些肿瘤的临床病程。通过直接测序筛选 sHGG 患者的 IDH 突变,通过甲基化特异性聚合酶链反应分析 MGMT 基因启动子状态。99 例患者中共有 48 例(48.5%)为继发性间变性神经胶质瘤(第 1 组),51 例为继发性胶质母细胞瘤(第 2 组)。所有 sHGG 患者和 IDH 突变患者恶性进展后的中位生存时间为 4 年,明显长于野生型 IDH 患者(1.2 年,p=0.009)。MGMT 启动子状态对患者的生存没有明显影响,第 1 组为 9.7 年比 6.1 年,甲基化比未甲基化启动子(p=0.330);第 2 组为 1.5 年比 1.6 年,甲基化比未甲基化启动子(p=0.829)。在我们的人群中,IDH 突变状态与 sGBM 患者的 PFS 或中位生存时间增加无关。然而,继发性间变性神经胶质瘤和 IDH 突变患者的预后明显改善。此外,IDH 突变是这些患者中比 MGMT 启动子状态更有力的预后标志物,无论是在 PFS 还是 MS 方面。

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