Publication Date
10-25-2024
Journal
Science Advances
DOI
10.1126/sciadv.adn4419
PMID
39441930
PMCID
PMC11498213
PubMedCentral® Posted Date
10-23-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Meningioma, Male, Female, DNA Methylation, Neoplasm Recurrence, Local, Middle Aged, Risk Factors, Meningeal Neoplasms, DNA Copy Number Variations, Aged, Adult, Gene Expression Regulation, Neoplastic, Epigenesis, Genetic
Abstract
An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex (P = 0.012), subtotal resection (P = 0.001), higher number of meningiomas on presentation (P = 0.017), and histopathological sheeting (P = 0.002). Multiomic analysis of primary meningiomas revealed that MRMs have greater copy number losses (P = 0.0313) and increased DNA methylation (P = 0.0155). In meningioma cells with knockdown of EDNRB, a locus with greater promoter methylation and decreased gene expression in MRMs had increased proliferation (P < 0.0001). MRM recurrences were found to be similar to primaries but have a greater burden of copy number gains (P < 0.0001) and increased methylation (P = 0.0045). This clinical and multiomic investigation of MRMs harbors implications for the future development of biomarkers and therapeutic agents for these challenging tumors.