Scholarlink

<p>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, <i>n</i> = 71 (54%)), Group B (<i>NF2</i> mutation/22q loss without high-risk CNAs, <i>n</i> = 45 (34%)), and Group C (high-risk CNAs, <i>n</i> = 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 (<i>P</i> = 0.023), and this remained significant even when the analysis was anatomically restricted to tumors located in the medial incisura and clivus (<i>P</i> = 0.0003). In multivariable analysis, Group C (<i>P</i> = 0.020, HR 6.60) and preoperative tumor volume &gt; 10 cc (<i>P</i> = 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integrated molecular and detailed anatomical profiling identifies a prognostically adverse subtype of posterior fossa meningiomas: high-risk copy number alterations are associated with midline predilection and predict poor prognosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月7日

查看全文
  • Yudai Hirano,
  • Satoru Miyawaki,
  • Yu Sakai,
  • Yu Teranishi,
  • Motoyuki Umekawa,
  • Takeru Hirata,
  • Shotaro Ogawa,
  • Daisuke Komura,
  • Hiroto Katoh,
  • Masako Ikemura,
  • Satoshi Koizumi,
  • Hideaki Ono,
  • Tetsuo Ushiku,
  • Shumpei Ishikawa,
  • Nobuhito Saito

摘要

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.