A team of Yale researchers, led by Zeynep Erson-Omay, PhD, assistant professor in the Department of Neurosurgery, and Murat Gunel, MD, chair of the Department of Neurosurgery, Sterling Professor of Neurosurgery, and professor of genetics and of neuroscience at Yale School of Medicine, has identified a previously unrecognized molecular subgroup of meningiomas defined by recurrent gene fusions involving FOS and FOSB genes. The discovery, published in Nature Communications, provides clinicians with an additional tool for treating one of the most common forms of brain tumors.
“Our labs, starting with Dr. Gunel’s lab in 2011, have been working on the genomic characterization of these brain tumors,” says Erson-Omay who, along with Gunel, is a member of Yale Cancer Center. “While progress has been made to identify the genetic markers associated with meningiomas, we still haven’t identified about 17% of them. This limits our ability to provide precision diagnosis and to develop targeted therapies.”
Meningiomas are the most common primary tumors found in the central nervous system. They represent more than one-third of all brain tumors and impact over 39,000 people in the United States every year. Many of these tumors are slow growing and can often be managed with surgery or radiation therapy. However, a significant subset of these tumors has shown unpredictable behavior, leading researchers to determine meningiomas are far more molecularly diverse than previously thought.
The Yale team focused their study on the FOS gene family which includes FOSB, a protein that regulates cell reproduction, separation, and transformation in humans.
“We compiled the profile of 1,232 meningioma cases from previously published cases to investigate where these FOS/FOSB fusion-driven meningiomas fall in the larger meningioma profile,” Erson-Omay explains. “Our study revealed that FOS/FOSB fusion cases form a distinct cluster with unique features.”
The study was conducted by a multidisciplinary team including experts in neurosurgery, genomics, computational biology, and pathology. Declan McGuone, FRCPath Neuro, MBBCh, associate professor in the Department of Pathology, led the histopathologic evaluation and characterization of these tumors. His team defined the tumors’ morphologic features and integrated the molecular findings into a 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 gene changes. The discovery of this fusion-defined subgroup offers new understanding of how meningiomas develop and establishes a foundation for future studies aimed at improving diagnosis and identifying subtype-specific vulnerabilities that may lead to improved treatments.
“One of the driving motivations for the study is the fact that there is currently no systemic or targeted treatment for these tumors,” Erson-Omay says. “Treatments have proved difficult to develop, so we hope that discovering these new subsets can pave the way for new treatments.”
Erson-Omay added that potential treatments developed from this new information would not be limited only to this type of brain tumor. “The alteration we’ve identified is not unique to meningiomas,” she says. “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.”