BIOM-60. UNDERSTANDING THE INTERSECTION OF RACE, SEX, AND GENOMIC PROFILES IN MENINGIOMA PATHOPHYSIOLOGY

Abstract BACKGROUND While meningioma incidence and outcomes vary by sex and race, the potential underlying molecular differences possibly contributing to these disparities are less understood. Herein, we explore the clinical and genomic characteristics of meningiomas across groups characterized by age and sex. METHODS We analyzed adult patients with primary meningiomas resected from 2012 to 2023. Patients underwent whole exome sequencing, and demographic data were categorized into four groups based on self-reported race and sex, which included White females, White Males, Black females, and Black males. The primary analyses involved comparisons of tumor characteristics, socioeconomic status (median zip code income, % with high school diploma, health insurance status, distance from hospital), genomics, and recurrence rates. RESULTS The study included 509 primary meningiomas. White females exhibited low-risk genomic profiles characterized by driver mutations in KLF4 (+/- TRAF7) (p=0.010) and POLR2A (p=0.045), with no associated CNVs (p=0.410). This benign molecular profile correlated with lower WHO grades (p=0.013) and a lower incidence of recurrence (p=0.0003). Black females had meningiomas enriched with Hedgehog pathway mutations (p=0.0035) and a predilection for the anterior skull base (p=0.034), leading to an increased risk of recurrence (p=0.026). White males showed an aggressive genomic profile, including chromosome 1p loss (p=0.025) and 10q loss (p=0.067), associated with a high risk of recurrence (p=0.0002). Black males had meningiomas with chromosome 14q loss (p=0.0002), the highest incidence of high-grade meningiomas (p=0.048), and a 4.5-fold increased risk of recurrence (OR 4.5 [1.6-11.8]; p=0.006). Black males also experienced the worst progression-free survival (HR 5.5 [2.5-12.4]; p<0.0001), independent of WHO grade, extent of resection, and socioeconomic status. CONCLUSIONS Each demographic has a distinct molecular profile that correlates with clinical behavior in a race and sex-specific manner. Black males are disproportionately affected by biologically aggressive meningiomas, leading to higher tumor grade and recurrence rates.