Hirano Yudai, Miyawaki Satoru, Sakai Yu, Teranishi Yu, Umekawa Motoyuki, Hirata Takeru, Ogawa Shotaro, Komura Daisuke, Katoh Hiroto, Ikemura Masako, Koizumi Satoshi, Ono Hideaki, Ushiku Tetsuo, Ishikawa Shumpei, Saito Nobuhito
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Acta Neuropathol Commun. 2025 Aug 7;13(1):168. doi: 10.1186/s40478-025-02083-z.
Anatomical localization of meningiomas has been increasingly linked to their genetic alterations. However, studies focusing specifically on the genomic landscape and clinical implications of posterior fossa meningiomas remain limited. In this study, we investigated the genetic, anatomical, and clinical characteristics of posterior fossa meningiomas, aiming to clarify the association between genetic alterations, precise tumor localization, and prognosis. Whole-exome sequencing was performed on 132 consecutive tumors to identify driver mutations and copy number alterations (CNAs). Tumor localization was carefully assessed based on dural attachment, arterial supply, and intraoperative findings. Based on driver mutations and CNAs, tumors were classified into three molecular groups: Group A (no Merlin pathway alterations, n = 71 (54%)), Group B (NF2 mutation/22q loss without high-risk CNAs, n = 45 (34%)), and Group C (high-risk CNAs, n = 16 (12%)). Notably, Group C showed a strong anatomical predilection, with 81% arising from midline structures, including the medial incisura and clivus. Group C tumors were significantly associated with poor progression-free survival following gross total resection (P = 0.023), and this remained significant even when the analysis was anatomically restricted to tumors located in the medial incisura and clivus (P = 0.0003). In multivariable analysis, Group C (P = 0.020, HR 6.60) and preoperative tumor volume > 10 cc (P = 0.044, HR 9.41) independently predicted poor prognosis. Overall, the results demonstrated that approximately 10% of posterior fossa meningiomas harbored high-risk CNAs, predominantly in midline locations, and were associated with worse clinical outcomes. CNA profiling in addition to the identification of driver mutations may provide a valuable tool for risk stratification and decision-making regarding adjuvant therapy in posterior fossa meningiomas.
脑膜瘤的解剖定位与其基因改变的关联日益紧密。然而，专门针对后颅窝脑膜瘤的基因组格局及临床意义的研究仍然有限。在本研究中，我们调查了后颅窝脑膜瘤的基因、解剖及临床特征，旨在阐明基因改变、精确肿瘤定位与预后之间的关联。对132例连续的肿瘤进行全外显子测序，以识别驱动突变和拷贝数改变（CNAs）。基于硬脑膜附着、动脉供应及术中所见仔细评估肿瘤定位。根据驱动突变和CNAs，将肿瘤分为三个分子组：A组（无Merlin通路改变，n = 71（54%））、B组（NF2突变/22q缺失且无高危CNAs，n = 45（34%））和C组（高危CNAs，n = 16（12%））。值得注意的是，C组显示出强烈的解剖学偏好，81%起源于中线结构，包括内侧小脑幕切迹和斜坡。C组肿瘤在全切术后与无进展生存期差显著相关（P = 0.023），即使在解剖学上仅限于内侧小脑幕切迹和斜坡的肿瘤进行分析时，这一关联仍显著（P = 0.0003）。在多变量分析中，C组（P = 0.020，HR 6.60）和术前肿瘤体积>10 cc（P = 0.044，HR 9.41）独立预测预后不良。总体而言，结果表明约10%的后颅窝脑膜瘤存在高危CNAs，主要位于中线位置，且与更差的临床结局相关。除了识别驱动突变外，CNA分析可能为后颅窝脑膜瘤辅助治疗的风险分层和决策提供有价值的工具。
