In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

与成人相比，脑膜瘤是儿童和青春期不常见的肿瘤。成人和儿童脑膜瘤在分子水平上是否存在差异尚不清楚。在这里，我们通过测序和 DNA 甲基化分析报告了 37 例小儿脑膜瘤的详细基因组分析。组织学上，该系列以具有攻击性行为的脑膜瘤亚型为主，70% 的患者患有 WHO II 级或 III 级脑膜瘤。最常见的细胞遗传学异常是 22 号染色体（23/37 [62%]）、1 号（9/37 [24%]）、18 号（7/37 [19%]）和 14 号（5/37 [14 %]）。NF2肿瘤改变表现出总体上增加的染色体不稳定性。DNA 甲基化谱的无监督聚类显示分为三组：指定的第 1 组由透明细胞和乳头状脑膜瘤组成，而第 2A 组主要包括非典型脑膜瘤，第 2B 组富含罕见的高级亚型（横纹肌样、脊索样样）。来自 NF2 患者的脑膜瘤仅聚集在第 1 组和第 2A 组中。与 105 个成人脑膜瘤的数据集相比，儿童脑膜瘤在很大程度上是分开分组的。34 种肿瘤的靶向 panel DNA 测序揭示了频繁的NF2改变，而在成人非NF2中发现的其他典型改变没有肿瘤。这些数据表明，小儿脑膜瘤的特征在于与成人肿瘤不同的分子特征。