Intraventricular meningiomas (IVMs) account for less than 5% of all intracranial meningiomas; hence their molecular phenotype remains unknown. In this study, we were interested whether genetic alterations in IVMs differ from meningiomas in other locations and analyzed our institutional series with respect to clinical and molecular characteristics. A total of 25 patients with surgical removal of an IVM at our department between 1986 and 2018 were identified from our institutional database. Median progression-free survival (PFS) was 79 months (range of 2-319 months) and PFS at 5 years was 86%. Corresponding tumor tissue was available for 18 patients including one matching recurrence and was subjected to targeted panel sequencing of 130 selected genes frequently mutated in brain cancers by applying a custom hybrid capture approach on a NextSeq500 instrument. Loss of chromosome 22q and 1p occurred frequently in 89 and 44% of cases. Deleterious NF2 mutations were found in 44% of IVMs (n = 8/18). In non-NF2-mutated IVMs, previously reported genetic alterations including TRAF7, AKT1, SMO, KLF4, PIK3CA, and TERT were lacking, suggesting alternative genes in the pathogenesis of non-NF2 IVMs. In silico analysis revealed possible damaging mutations of APC, GABRA6, GSE1, KDR, and two SMO missense mutations differing from previously reported ones. Interestingly, all WHO°II IVMs (n = 3) harbored SMARCB1 and SMARCA4 mutations, indicating a role of the SWI/SNF chromatin remodeling complex in aggressive IVMs.

中文翻译：

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脑室内脑膜瘤经常携带NF2突变，但在TRAF7，AKT1，SMO，KLF4，PIK3CA和TERT中缺乏常见的遗传改变。

脑室内脑膜瘤（IVM）占所有颅内脑膜瘤的比例不到5％；因此，它们的分子表型仍然未知。在这项研究中，我们感兴趣的是IVM中的遗传改变是否与其他地区的脑膜瘤有所不同，并就临床和分子特征分析了我们的机构研究系列。从我们的机构数据库中识别出了1986年至2018年间我科共25例外科手术切除IVM的患者。中位无进展生存期（PFS）为79个月（2-319个月），5年时无进展生存率为86％。对应的肿瘤组织可供18名患者使用，包括一次匹配的复发，并通过在NextSeq500仪器上应用定制的杂种捕获方法，对130种在脑癌中经常发生突变的基因进行了针对性的靶点测序。89％和44％的病例频繁发生22q和1p染色体丢失。在44％的IVM中发现了有害的NF2突变（n = 8/18）。在非NF2突变的IVM中，先前报道的遗传改变包括TRAF7，AKT1，SMO，KLF4，PIK3CA和TERT缺乏，这提示非NF2 IVM的发病机制中存在替代基因。在计算机分析中发现了可能破坏性的APC，GABRA6，GSE1，KDR突变，以及两个SMO错义突变，这些突变不同于先前报道的突变。有趣的是，所有WHOII II IVM（n = 3）都携带SMARCB1和SMARCA4突变，