Integra Foundation Award: Molecular Profile of Meningiomas Differ Among Sex and Races

Introduction: While meningiomas are more commonly found in females, males are more likely to harbor those of higher grade. We have also found Black patients have an increased risk of higher grade meningiomas with worse outcome compared to White patients. Here, we investigated how race and sex influence outcome and searched for differences in the molecular profile of these tumors.

Methods: We reviewed patients with confirmed meningioma who underwent surgical resection and whole exome sequencing. We defined the following categories of race and sex: Black Male, White male, Black female, White female and then compared for patient demographics, tumor characteristics, somatic driver mutations, copy number variations (CNVs), mutational signatures for mismatch repair (MMR) and microsatellite instability (MSI), recurrence, and progression-free survival (PFS).

Results: 482 patients met inclusion criteria for the study. Black males were more likely to have higher grade tumors (OR 3.1[1.1-9.1];p=0.0385), NF2 driver mutation (OR 5.3[1.5-21.6]; p=0.0087), 14q loss (OR 6.6[1.2-51.0]; p=0.0276), and 19p loss compared to Black females. Compared to White females, Black males were more likely to harbor higher grade meningiomas (OR 2.7[1.2-6.6];p=0.0132), NF2 driver mutations (OR 3.1[1.1-10.2]%;p=0.034) and 14q loss (OR 6.6[1.2-51.0];p=0.009). There were no differences in driver mutations or CNV’s between Black males and White males. Mutational signatures associated with MMR deficiency (SBS20 and SBS21) only occurred in Black patients. Consequently, Black males had a 7-times increased risk of recurrence compared to White females (OR 7.1[2.5-19.2];p=0.0004) and had lower PFS compared to both White Females and White Males (HR 8.1[3.4-19.4];p < 0.0001).

Conclusion : We demonstrate Black Males with meningiomas are more likely to have higher rates of recurrence with the lowest PFS independent of WHO grade. Indeed, their tumors are more often harbor somatic NF2 driver mutations with high risk CNV’s and mutational signatures associated with MMR deficiency and microsatellite instability. Further insights into genetic ancestry risk may allow for more personalized treatment of this population.