Comparative genomic analysis of driver mutations in matched primary and recurrent meningiomas

Abstract

A significant proportion of low-grade WHO grade I and higher-grade WHO grade II or III meningiomas are at risk to develop post-resection recurrence. Though recent studies investigated genomic alterations within histological subtypes of meningiomas, few have compared genomic profiles of primary meningiomas matched to their recurrences. The present study aimed to identify oncogenic driver mutations that may indicate risk of meningioma recurrence and aggressive clinical course. Seventeen patients treated for low-grade (n = 8) or high-grade (n = 9) meningioma and underwent both primary and recurrent resection between 2007–2017 were reviewed. Tumor specimens (n = 38) underwent genomic sequencing of known oncogenic driver mutations. Primary and recurrent tumors were compared using matched-pair analyses for mutational associations with clinical outcomes including functional status, progression-free survival (PFS) and overall survival (OS). Most common driver mutations included POLE and NF2. There was no enrichment for any driver mutation from primary to recurrent tumor specimen. NF2 mutant meningiomas were associated with larger tumor size (8-fold increase), presence of vasogenic edema, and higher mitotic proliferation on univariate and independently on multivariate regression (p’s < 0.05) after controlling for preoperative and tumor features. Tumors with POLE driver mutations were associated with decreased functional status at last postoperative follow-up (p = 0.022) relative to presentation. Mutation status was not associated with PFS or OS on multivariate Cox regression, but rather with grade of resection (p = 0.046) for PFS. While primary and recurrent tumors exhibited similar driver mutations within patients, the identification of driver mutations associated with clinical outcomes is crucial for guiding potential targeted treatments in recurrent meningiomas.