Hidden Genetic Subgroup Sheds New Light on Brain Tumors

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. They account for more than one-third of all brain tumors and affect over 39,000 people in the United States each year. However, unpredictable behavior in a subset of meningiomas complicates diagnosis and treatment planning, and despite extensive study, approximately 17% lack known genetic drivers. New findings have now identified a previously unrecognized molecular subgroup of meningiomas, offering clinicians additional insight that may support more informed treatment decisions.

The discovery was made by a multidisciplinary team at Yale University (New Haven, CT, USA) spanning neurosurgery, genomics, computational biology, and pathology. The newly identified subgroup is driven by fusions in the FOS gene family, which includes FOSB, a protein that regulates cell reproduction, separation, and transformation in humans. These findings were reported in a study recently published in Nature Communications. 

The researchers compiled genomic profiles from 1,232 meningioma cases across previously published datasets to assess how FOS/FOSB fusion–driven tumors fit within the broader molecular landscape. The analysis showed that FOS/FOSB fusion–positive cases form a distinct molecular cluster with unique biological features. Histopathologic evaluation was then performed to define the tumors’ morphologic characteristics and integrate the molecular findings into a unified diagnostic and clinical framework. 

This work expands the current molecular classification of meningiomas and addresses a major gap in understanding tumors that lack known key genetic alterations. Identification of this fusion-defined subgroup provides new insight into meningioma development and lays the groundwork for future studies aimed at improving diagnostic precision and uncovering subtype-specific vulnerabilities that could inform targeted therapies.     

“One of the driving motivations for the study is the fact that there is currently no systemic or targeted treatment for these tumors,” said Zeynep Erson-Omay, PhD, assistant professor in the Department of Neurosurgery at Yale School of Medicine. “Treatments have proved difficult to develop, so we hope that discovering these new subsets can pave the way for new treatments.” 

“The alteration we’ve identified is not unique to meningiomas,” added Dr. Erson-Omay. “There are other soft-tissue and bone-tissue tumor types that have similar genetic alterations. Our hope is that any treatments developed from these findings can have a broader impact beyond just meningiomas.”

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