Prospective consecutive genomic profiling defines the distribution of meningioma molecular alterations across demographic groups.

BACKGROUND

Molecular profiling is increasingly important for risk stratification and individualization of treatment recommendations for patients with meningioma. Prior investigations have established the genomic architecture of meningioma, but the distribution of meningioma copy number alterations (CNAs) and short somatic variants (SSVs) across demographic groups is incompletely understood. Here we define a prospective, consecutive benchmark for meningioma CNAs and SSVs across demographic groups.

METHODS

Prospective next-generation DNA sequencing was performed on 1,104 tumor samples from 1,044 consecutive patients who were treated for meningioma or whose meningiomas underwent molecular testing at a large academic medical center in a major US city from 2019 to 2025. Univariate and multivariate regression analyses were performed to evaluate associations between demographic characteristics, CNAs, and SSVs.

RESULTS

Meningiomas from Asian males were enriched in high-risk molecular features, including (1) copy number deletion of chromosomes 1p, 6q, and 14q, (2) copy number gain of chromosome 1q, (3) chromosome 1p/22q codeletion or co-occurrent 1p loss/1q gain, and (4) CDKN2A/B homozygous deletion. In contrast, meningiomas from females were enriched in low-risk molecular features, including SSVs in TRAF7, AKT1, and PIK3CA. The molecular architecture of meningiomas from Hispanic and non-Hispanic White individuals appeared similar, though Hispanic ethnicity was a unique independent predictor of low-grade disease.

CONCLUSIONS

In this US-based cohort, the distribution of meningioma CNAs and SSVs varies across demographic groups. Asian males appear to have an increased risk of clinically aggressive meningioma due to enrichment in high-risk molecular features that were previously unappreciated in this patient population. Molecularly favorable meningiomas are more common in females, and low-grade meningiomas are more common in Hispanic individuals.