儿童和年轻发病脑膜瘤中不同的分子亚群需要年龄适应的风险分层
Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification.
摘要(中文译文)
儿童及青少年/年轻成人脑膜瘤在生物学和临床特征方面认识不足，风险分层很大程度上沿用成人肿瘤的标准。我们通过整合组织病理学和分子谱分析，分析了293例0-39岁患者的肿瘤。青年起病脑膜瘤富含NF2和SMARCE1改变，呈现以拷贝数获得为主的格局，包括反复出现的17q染色体获得，而成人经典高危特征（如1p染色体缺失）缺乏预后意义。源自成人的预后框架，包括WHO分级、基于甲基化的分层和整合风险评分，均无法预测≤21岁患者的进展。肿瘤可分为以SMARCE1、NF2和BAP1改变为定义、随年龄富集的表观遗传簇。在NF2改变的肿瘤中，Merlin失活模式受胚系状态和共现拷贝数变异影响，勾勒出生物学上不同的亚群。在≤21岁患者中，切除范围是结局的主要预测因素，而分子特征可进一步细化风险评估。这些发现将儿童和年轻成人脑膜瘤定义为一个独特的分子实体，并支持整合分子特征与强临床决定因素的年龄适应性风险细化。
Abstract
Meningiomas in pediatric and adolescent/young adult patients are poorly characterized biologically and clinically, and risk stratification is largely extrapolated from adult tumors. We analyze 293 tumors from patients aged 0-39 years using integrated histopathological and molecular profiling. Youth-onset meningiomas are enriched for NF2 and SMARCE1 alterations and exhibit a gain-dominated copy-number landscape, including recurrent chr17q gain, whereas canonical adult high-risk features, such as chr1p loss, lack prognostic significance. Adult-derived prognostic frameworks, including WHO grade, methylation-based stratification and integrated risk scores, fail to predict progression in patients ≤21 years of age. Tumors segregate into age-enriched epigenetic clusters defined by SMARCE1, NF2 and BAP1 alterations. Among NF2-altered tumors, patterns of Merlin inactivation, shaped by germline status and co-occurring copy-number variations, delineate biologically divergent subsets. In patients ≤21 years, extent of resection is the dominant predictor of outcome, while molecular features further refine risk assessment. These findings define pediatric and young adult meningiomas as a distinct molecular entity and support age-adapted risk refinement that integrates molecular features with strong clinical determinants.
如何引用
AMA
Natalie Berghaus, Arnault Tauziède-Espariat, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Kirsten Göbel, et al. Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification.. Nature communications. 2026; doi:10.1038/s41467-026-75357-2.
APA
Natalie Berghaus, Arnault Tauziède-Espariat, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Kirsten Göbel, et al (2026). Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification.. Nature communications. https://doi.org/10.1038/s41467-026-75357-2
GB/T 7714
Natalie Berghaus, Arnault Tauziède-Espariat, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Kirsten Göbel, et al. Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification.[J]. Nature communications, 2026 doi:10.1038/s41467-026-75357-2.
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