Molecular classification of radiation-induced meningiomas.

PURPOSE: Radiation-induced meningiomas (RIMs) are an uncommon late complication of cranial irradiation that frequently display aggressive behavior. Although recent genomic and epigenomic studies have redefined sporadic meningiomas into four molecular groups with distinct biological and clinical characteristics, the same analysis has not yet been conducted on RIMs. This study sought to contextualize RIMs within the current methylation-based meningioma classification. METHODS: DNA methylation data from RIMs (n = 20) were integrated with a reference cohort of sporadic (n = 121) meningiomas previously used to define molecular subgroups. Molecular group membership was assigned using a supervised machine-learning approach. Copy-number alterations and pathway enrichment analyses were derived from methylation data, and clinical features were compared between RIMs and sporadic meningiomas. RESULTS: Supervised molecular classification assigned 70% RIMs to the hypermetabolic subtype. The RIM cohort demonstrated broad DNA hypomethylation enriched for metabolic and biosynthetic pathways. Copy-number profiling revealed widespread chromosomal instability, including recurrent 22q loss involving NF2 and SMARCB1 as well as PTEN, MYB, and C19MC, consistent with the copy number alterations observed in hypermetabolic meningiomas. CONCLUSIONS: RIMs predominantly align with the hypermetabolic molecular group, characterized by metabolic pathway activation and genomic instability. This distribution indicates a distinct molecular profile compared with sporadic meningiomas.