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<p>Meningiomas are the most common primary tumors of the central nervous system and are typically treated with surgery or radiation, as targeted therapies remain limited. Despite extensive study, seventeen percent of meningiomas lack known genetic drivers. Our analysis of meningiomas without driver mutations or major chromosomal alterations identifies a subset with recurrent genomic rearrangements involving the <i>FOS</i> and <i>FOSB</i> genes. These tumors exhibit elevated FOS/FOSB protein levels and retain meningothelial lineage. Here we show that <i>FOS</i>/<i>FOSB</i> fusion-positive meningiomas represent a distinct molecular subgroup, defined by unique gene expression patterns, including activation of AP-1 target genes and signatures resembling preadipocyte-like and mast cell–associated profiles. Clinically, these tumors display low-grade behavior and DNA methylation profiles consistent with benign subtypes. Our findings identify a meningioma subgroup with distinct genetic, transcriptomic, and clinical features, expanding the molecular classification of meningiomas and opening new avenues for targeted treatment strategies.</p>

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Subgroup of meningiomas involving FOS and FOSB gene fusions

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月26日

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  • Kanat Yalcin,
  • Hasan Alanya,
  • Batur Gultekin,
  • Diego Samper Figuera,
  • Tanyeri Barak,
  • Danielle F. Miyagishima,
  • Mark W. Youngblood,
  • Mateo Gomez Hjerthen,
  • Amos Brooks,
  • Natalia Samuel Lopez,
  • Joseph O’Brien,
  • Miguel Millares Chavez,
  • Alper Dincer,
  • Hao Wu,
  • S. Bulent Omay,
  • Katsuhito Yasuno,
  • Kaya Bilguvar,
  • A. Gulhan Ercan-Sencicek,
  • Ketu Mishra-Gorur,
  • Declan McGuone,
  • Jennifer Moliterno,
  • Murat Gunel,
  • E. Zeynep Erson-Omay

摘要

Meningiomas are the most common primary tumors of the central nervous system and are typically treated with surgery or radiation, as targeted therapies remain limited. Despite extensive study, seventeen percent of meningiomas lack known genetic drivers. Our analysis of meningiomas without driver mutations or major chromosomal alterations identifies a subset with recurrent genomic rearrangements involving the FOS and FOSB genes. These tumors exhibit elevated FOS/FOSB protein levels and retain meningothelial lineage. Here we show that FOS/FOSB fusion-positive meningiomas represent a distinct molecular subgroup, defined by unique gene expression patterns, including activation of AP-1 target genes and signatures resembling preadipocyte-like and mast cell–associated profiles. Clinically, these tumors display low-grade behavior and DNA methylation profiles consistent with benign subtypes. Our findings identify a meningioma subgroup with distinct genetic, transcriptomic, and clinical features, expanding the molecular classification of meningiomas and opening new avenues for targeted treatment strategies.