Subgroup of meningiomas involving FOS and FOSB gene fusions

Area of Science:

• Neuro-oncology
• Genomics
• Molecular Biology

Background:

• Meningiomas are the most common primary central nervous system tumors.
• Current treatments like surgery and radiation have limitations, and targeted therapies are scarce.
• Seventeen percent of meningiomas lack identified genetic drivers.

Purpose of the Study:

• To identify novel molecular subgroups within meningiomas lacking known genetic drivers.
• To characterize the genetic, transcriptomic, and clinical features of a newly identified meningioma subset.
• To explore potential new therapeutic targets for meningiomas.

Main Methods:

• Genomic analysis of meningiomas without driver mutations or major chromosomal alterations.
• Identification of recurrent genomic rearrangements involving FOS and FOSB genes.
• Gene expression profiling and DNA methylation analysis.

Main Results:

• A distinct molecular subgroup of meningiomas with recurrent FOS/FOSB gene rearrangements was identified.
• These tumors showed elevated FOS/FOSB protein levels and retained meningothelial lineage.
• Distinct gene expression patterns, including AP-1 target gene activation and preadipocyte/mast cell-associated profiles, were observed.
• Clinically, these tumors exhibited low-grade behavior and benign DNA methylation profiles.

Conclusions:

• FOS/FOSB fusion-positive meningiomas represent a unique molecular subgroup.
• This subgroup is defined by specific genetic alterations, gene expression signatures, and clinical characteristics.
• The findings expand the molecular classification of meningiomas and suggest potential avenues for targeted treatment strategies.