The Genomic Profiles and Clinical Manifestations of Sporadic Meningiomas Vary Amongst Racial and Ethnic Groups

Introduction: While socioeconomic factors for racial disparities amongst sporadic meningioma patients have been explored, potential biological differences in patients of different races/ethnicities and genetic ancestries are poorly understood. We sought to identify whether characteristics and outcomes differ amongst meningioma patients of different self-reported races/ethnicities and genetic ancestries.

Methods: Patients who underwent surgery for sporadic meningioma were eligible. Self-reported race/ethnicity was collected retrospectively, and genetic ancestry was determined using whole exome sequencing (WES) on a subset of patients.

Results: 523 intracranial meningiomas from 470 patients were included. The cohort was 72.7% White, 14.0% Black, 9.5% Hispanic. Hispanics were significantly younger at diagnosis (p < 0.001) and surgery (p < 0.001) and more likely to be symptomatic (vision changes (p=0.003) and headaches (p < 0.001)). Blacks had a higher percentage of anterior skull base tumors (p=0.004) and somatic Hedgehog mutations (p=0.008). Blacks exhibited more aggressive tumors, with higher grade (p=0.044) and chromosomal instability (p=0.022); meningiomas of Hispanics were less likely to have the aggressive genomic feature of chromosome 1p deletion (p=0.017). Blacks experienced more recurrence (p=0.046) and shorter progression-free survival (PFS) (p=0.047) despite similar extent of resection (EOR) (p=.736). Ancestries other than non-Jewish European correlated with decreased PFS (HR=3.56;p=0.0057) and West African (HR=3.75;p=0.034) was associated with decreased PFS. Overall survival (OS) was significantly different between self-reported groups (p=0.039), with Hispanics having the greatest OS followed by Whites, then Blacks.

Conclusion : Overall, self-reported Blacks have higher-grade meningiomas with underlying chromosomal instability and a higher prevalence of HH mutations. They have worse clinical outcomes, with increased recurrence and worse PFS and OS, despite similar EOR. Correspondingly, West African genetic ancestry is indeed associated with worse PFS. Hispanics, however, present earliest and have better survival. Further genomic, epigenomic, and environmental studies focusing on the inherited versus somatic basis of these observed differences are needed and can help guide more personalized meningioma care.