TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas
TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas
复制标题
DOI：
10.1007/s11060-015-1999-3
复制
发表时间：
2016-02-01
影响因子：
3.9
通讯作者：
Sanson, Marc
中科院分区：
文献类型：
--
作者：
Nencha, Umberto;Rahimian, Amithys;Sanson, Marc
TERT 启动子（TERTp）突变是胶质母细胞瘤中最常见的突变。它为 Ets/TCF 转录因子创建了一个假定的结合位点，增强了端粒酶的表达和活性，而 rs2853669 变体则破坏了另一个 Ets/TCF 结合。我们在此探讨这两种改变之间的相互作用、肿瘤基因组谱及其对预后的影响。确定了 TERTp 和 rs2853669 状态，并面对结果和分子谱，即染色体 10q 丢失、CDKN2A 缺失、IDH 突变、EGFR 扩增、MGMT 启动子甲基化。选择了 651 例胶质母细胞瘤（性别比 = 1.35，中位年龄 60.4 岁，中位生存期 13.5 个月）。在 481 名患者 (74%) 中发现的 TERTp 突变与 rs2853669 基因型无关。 TERTp 突变（而非 rs2853669 状态）与年龄较大相关（61.4 岁与 52.8 岁）。 rs2853669 状态对突变 TERTp 或野生型 TERTp 的总生存 (OS) 没有影响。 rs2736100 (TERT, 5q15.33) 和 rs192011116 (TERC, 3q26.2) 状态均对生存没有任何影响，也未显示与 TERTp 突变有任何关联。 TERTp 突变与 EGFR 扩增、染色体 10q 丢失、CDKN2A 缺失和 IDH wt 相关。 EGFR 扩增与 TERTp 突变 GBM 的更好结果相关，而 TERTp WT 的结果较差。这项研究是对 TERTp 突变和 rs2853669 多态性进行的最大规模的分析，但未能发现 rs2853669 的任何预后影响。它证实了 EGFR 扩增对 TERTp 状态的双重预后影响。
TERT promoter (TERTp) mutation is the most common mutation in glioblastomas. It creates a putative binding site for Ets/TCF transcription factors, enhancing telomerase expression and activity, whereas the rs2853669 variant disrupts another Ets/TCF binding. We explore here the interaction between these two alterations, tumor genomic profile and the impact on prognosis. The TERTp and rs2853669 statuses were determined and confronted with the outcome and molecular profile, i.e., loss of chromosome 10q, CDKN2A deletion, IDH mutation, EGFR amplification, MGMT promoter methylation. 651 glioblastomas were selected (sex ratio = 1.35, median age 60.4 years, median survival 13.5 months). The TERTp mutation found in 481 patients (74 %) was independent from rs2853669 genotypes. TERTp mutation, but not rs2853669 status, was associated with older age (61.4 vs. 52.8 years). rs2853669 status had no impact on overall survival (OS) either in mutated TERTp or wild-type TERTp. Neither rs2736100 (TERT, 5q15.33) nor rs192011116 (TERC, 3q26.2) status had any impact on survival or showed any association with a TERTp mutation. The TERTp mutation was associated with EGFR amplification chromosome 10q loss, CDKN2A deletion and IDH wt. EGFR amplification was associated with a better outcome in TERTp mutated GBM, and a worse outcome in TERTp WT. This study-the largest analyzing the TERTp mutation and the rs2853669 polymorphism-fails to find any prognostic impact of rs2853669. It confirms the dual prognostic impact of EGFR amplification depending on TERTp status.