Subgroup of meningiomas involving FOS and FOSB gene fusions

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 () and E. Zeynep Erson-Omay ()
Additional contact information
Kanat Yalcin: Yale School of Medicine, Department of Neurosurgery
Hasan Alanya: Yale School of Medicine, Department of Neurosurgery
Batur Gultekin: Yale School of Medicine, Department of Neurosurgery
Diego Samper Figuera: Yale School of Medicine, Department of Neurosurgery
Tanyeri Barak: Yale School of Medicine, Department of Neurosurgery
Danielle F. Miyagishima: Yale School of Medicine, Department of Neurosurgery
Mark W. Youngblood: Northwestern University, Department of Neurosurgery, Feinberg School of Medicine
Mateo Gomez Hjerthen: Northwestern University, Department of Neurosurgery, Feinberg School of Medicine
Amos Brooks: Yale School of Medicine, Department of Pathology
Natalia Samuel Lopez: Yale School of Medicine, Department of Neurosurgery
Joseph O’Brien: Yale School of Medicine, Department of Neurosurgery
Miguel Millares Chavez: Yale School of Medicine, Department of Neurosurgery
Alper Dincer: Tufts Medical Center, Department of Neurosurgery
Hao Wu: Yale School of Medicine, Department of Pathology
S. Bulent Omay: Yale School of Medicine, Department of Neurosurgery
Katsuhito Yasuno: Yale School of Medicine, Department of Neurosurgery
Kaya Bilguvar: Yale School of Medicine, Department of Neurosurgery
A. Gulhan Ercan-Sencicek: Yale School of Medicine, Department of Neurosurgery
Ketu Mishra-Gorur: Yale School of Medicine, Department of Neurosurgery
Declan McGuone: Yale School of Medicine, Department of Pathology
Jennifer Moliterno: Yale School of Medicine, Department of Neurosurgery
Murat Gunel: Yale School of Medicine, Department of Neurosurgery
E. Zeynep Erson-Omay: Yale School of Medicine, Department of Neurosurgery

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-65549-7

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