TERT Alterations in Progressive Treatment-Resistant Meningiomas
TERT Alterations in Progressive Treatment-Resistant Meningiomas
复制标题
DOI：
10.1093/neuros/nyy154
复制
发表时间：
2018-09-01
期刊：
影响因子：
4.8
通讯作者：
Cahill, Daniel P.
中科院分区：
文献类型：
--
作者：
Juratli, Tareq A.;Brastianos, Priscilla K.;Cahill, Daniel P.
脑膜瘤是最常见的原发脑肿瘤。1虽然大多数是生长缓慢的WHO(世界卫生组织)I级肿瘤，并被认为是良性的，但这些肿瘤中有很大一部分是非典型(II)或恶性(III)，自然病史较差。2脑膜瘤的初始标准治疗是手术切除，然后是复发、不典型或恶性脑膜瘤的放射治疗。然而，该病治疗后的临床病程明显不同：虽然大多数低级别脑膜瘤在切除后不会复发，但不典型和间变性脑膜瘤的复发是常见的。令人遗憾的是，目前还没有标准的治疗方法来为手术或放疗后出现肿瘤进展的脑膜瘤患者提供治疗。事实上，化疗的证据基础很差，导致受影响患者的发病率和死亡率增加。3因此，有一种尚未得到满足的需求，即更好地识别具有侵袭性临床病程的进展性脑膜瘤的风险患者。除了22号染色体上长期存在的NF2改变外，到目前为止，人们对促进脑膜瘤复发和进展的遗传病因和分子驱动因素知之甚少。在最近的几项非NF2 WHO I级脑膜瘤的基因组测序研究中，发现了SMO、AKT1、KLF4和TRAF7的频繁突变。4-6相反，大多数高级别脑膜瘤的研究一致地报告了一种异质性突变谱，很少有反复突变。
Meningiomas are the most common primary brain neoplasms. 1 While the majority are slow-growing WHO (World Health Organization) grade I tumors and are considered benign, a substantial fraction of these tumors is atypical (II) or malignant (III) with less-favorable natural history. 2 Initial standard-of-care therapy for meningiomas is surgical resection, followed by radiation in recurrent, atypical, or malignant meningiomas. Nevertheless, the posttreatment clinical course of the disease is remarkably heterogeneous: While most low-grade meningiomas do not recur after resection, recurrence in atypical and anaplastic meningiomas is frequent. Distressingly, there is currently no standard therapy to offer meningioma patients who show tumor progression after surgery or radiation. Indeed, the evidence base for chemotherapy is poor, resulting in substantial morbidity and increased mortality of affected patients. 3 Therefore, there is an unmet need to better identify patients who are at risk to develop progressive meningiomas with aggressive clinical course.Besides the long-established NF2 alterations on chromosome 22, to date little is known about the genetic etiology and the molecular drivers that promote meningioma recurrence and progression. In several recent genomic sequencing studies of non-NF2 WHO grade I meningiomas, frequent mutations in SMO, AKT1, KLF4, and TRAF7 were found. 4-6 In contrast, most studies in higher grade meningiomas consistently reported a heterogeneous mutation spectrum with few recurrently mutated