Subgroup of meningiomas involving FOS and FOSB gene fusions

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.

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Publication Details

Journal
Nature Communications
Published
2025-11-26
DOI
https://doi.org/10.1038/s41467-025-65549-7
Primary Topic
Meningioma and schwannoma management
Type
article
Field-Weighted Citation Impact
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article

Subgroup of meningiomas involving FOS and FOSB gene fusions

D Figuera, Jennifer Moliterno, Danielle Miyagishima, Katsuhito Yasuno et al.
Nature Communications
Meningioma and schwannoma management
article

Subgroup of meningiomas involving FOS and FOSB gene fusions

D Figuera, Jennifer Moliterno, Danielle Miyagishima, Katsuhito Yasuno, Murat Günel, Declan McGuone, Joseph O’Brien, A. Gulhan Ercan‐Sencicek, Mark W. Youngblood, Natalia Vila López, Amos Brooks, E. Zeynep Erson‐Omay, Sacit Bulent Omay, Ketu Mishra-Gorur, Tanyeri Barak, Kaya Bilgüvar, Miguel Millares Chavez, Hao Wu, Kanat Yalcin, Hasan Alanya, Batur Gültekin, Alper Dincer, Mateo Gomez Hjerthen
article en

Abstract

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.

Nature CommunicationsVol. 16(1)
Northwestern University (US), Tufts Medical Center (US), Yale Cancer Center (US), Yale University (US), Kent Hastanesi (TR)
Openalex Percentile: Top 52%
Meningioma and schwannoma management
DOIOpen Access PDFOpenAlex
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