High Incidence of Activating TERT Promoter Mutations in Meningiomas Undergoing Malignant Progression
High Incidence of Activating TERT Promoter Mutations in Meningiomas Undergoing Malignant Progression
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DOI：
10.1111/bpa.12110
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发表时间：
2014-03-01
期刊：
影响因子：
6.4
通讯作者：
Kalamarides, Michel
中科院分区：
文献类型：
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作者：
Goutagny, Stephane;Nault, Jean C.;Kalamarides, Michel
脑膜瘤是常见的中枢神经系统肿瘤。世界卫生组织（WHO）定义了三个等级，预测复发的风险。这些肿瘤可以经常复发，有时会发生恶性转化。端粒长度的维持是恶性进展中的关键过程，并且最近在各种类型的癌症中鉴定了TERT启动子的突变。我们对来自73名患者的85个脑膜瘤的TERT启动子进行了测序。我们发现在经历恶性组织学进展的脑膜瘤患者中，TERT启动子突变的发生率很高（28%，n=5/18例患者）。在这组组织学进展的患者中，在最低和最高级别的肿瘤中，以及在NF 2突变和非突变的样本中均发现了TERT启动子突变。相反，在35例无复发或进展的脑膜瘤中发现了一个突变，属于不同的组织学分级。这个样本是一个侵袭性脑膜瘤，病人在手术后不久死亡。有趣的是，显示复发而无组织学进展的肿瘤没有突变为TERT启动子（n=20）。最后，TERT启动子突变与TERT表达的显著增加相关。因此，TERT启动子突变是参与脑膜瘤恶性进展的关键遗传改变，可用作识别脑膜瘤恶变风险的生物标志物。
Meningiomas are common central nervous system tumors. The World Health Organization (WHO) defines three grades, predictive of the risk of recurrence. These tumors can relapse frequently and sometimes undergo malignant transformation. Maintenance of telomere length is a key process in malignant progression, and mutations in TERT promoter have recently been identified in various types of cancer. We sequenced the TERT promoter in 85 meningiomas from 73 patients. We found a high incidence of TERT promoter mutations in patients with meningiomas undergoing malignant histological progression (28%, n=5/18 patients). In this subset of patients with histological progression, TERT promoter mutations were found in both the lowest and the highest grade tumors, and in both NF2-mutated and nonmutated samples. In contrast, one mutation was identified in 35 meningiomas without recurrence or progression, belonging to various histological grades. This sample was an aggressive meningioma in a patient who died shortly after surgery. Interestingly, tumors showing relapse without histological progression were not mutated for TERT promoter (n=20). Finally, TERT promoter mutations were associated with a marked increase in TERT expression. Thus, TERT promoter mutations are pivotal genetic alterations involved in malignant progression of meningiomas and could be used as a biomarker to identify meningiomas at risk of malignant transformation.