Charting the Genomic Landscape of Meningiomas

By profiling the molecular features of meningioma, scientists are uncovering new biomarkers predicting how these brain tumors might respond to therapy and new potential therapeutic approaches.

Now, researchers at UC San Francisco report on the genomic landscape of meningioma in one of the largest prospectively collected datasets to date. Their findings, published in JAMA Oncology, provide a much-needed point of reference to guide evolving diagnostic criteria and the design of clinical trials for the most common type of brain tumor.

“As we increasingly move towards precision medicine clinical trials, understanding how likely or not a particular molecular alteration is within the general population is essential for understanding if a trial to target or leverage that alteration is feasible,” David Raleigh, MD, PhD, the director of the UCSF Translational Meningioma Program, a principal investigator at the UCSF Brain Tumor Center, and the study’s senior author, said.

A clearer picture of how frequently certain DNA mutations occur, he added, helps researchers select the right type of clinical trial they need to conduct to get meaningful outcomes for patients and choose appropriate inclusion and exclusion criteria.

At UCSF, all patients with a meningioma undergoing surgery began having their tumors sequenced using the UCSF500 Cancer Gene Panel in 2019. By analyzing next-generation DNA sequencing results from 1,104 consecutive meningioma samples collected between January 2019 to April 2025, Raleigh and his colleagues were able to get a more representative view of the prevalence of molecular alternations present in meningiomas.

Their analysis identified several new genomic alternations associated with an elevated tumor mutation burden, a biomarker that typically correlates with a better response to immunotherapy in other types of cancers. Raleigh says that these findings provide a framework for designing more clinical to test whether the same may be true in meningioma.

They further demonstrated that patients of Asian ancestry were more likely than white or Hispanic individuals to be diagnosed with grade 3 meningiomas. Their tumors were also more likely to be enriched with molecular alternations associated with a poor disease prognosis, such as genomic variants in the CDKN2A/B genes or duplications and deletions of long stretches of DNA (known as copy number alternations).

However, the UCSF team showed that CDKN2A/B promoter variants, as well as TERT promoter variants, were only found in about 3 percent of patients in this cohort. This is a smaller incidence than previous retrospective studies and indicates, that although current diagnostic guidelines recommend testing for these variants in high-grade tumors, they may not be the best indicators of aggressive disease due to their rarity.

To Raleigh, these results highlight how genetic alternations are not the only molecular feature important for determining which meningiomas would be more likely to be recur or not respond to treatment. Other factors like DNA methylation status and gene expression risk scores will continue to play a big role in these assessments.

Continued funding and collaboration through the Cancer Health Outcomes Specialized Program of Research Excellence (SPORE) will also help support larger, multi-institutional studies across patient populations.

And with a molecular framework to understand the biology of meningioma, Raleigh says, researchers can devise better strategies to treat these tumors.

Reference: Nguyen MP, Mirchia K, Braman BC, et al. Prospective Genomic Profiling of Consecutive Meningiomas. JAMA Oncol. Published online April 09, 2026. doi:10.1001/jamaoncol.2026.0507