EPCO-31. CLINICALLY APPLICABLE MOLECULAR GROUPING OF INTRACRANIAL MENINGIOMAS BASED ON HIGH-RISK COPY NUMBER ALTERATIONS AND <i>NF2</i> /22Q STATUS

Abstract BACKGROUND The 2021 WHO classification of meningiomas incorporated molecular markers such as CDKN2A/B homozygous deletion and TERT promoter (pTERT) mutations as diagnostic criteria for grade 3 tumors. Although large-scale multi-omics studies have revealed the biological heterogeneity of meningiomas, their clinical implementation remains limited. METHODS This study included intracranial meningiomas surgically resected between 1999 and 2024. Whole-exome sequencing was performed to identify driver mutations and arm-level copy number alterations (CNAs). Tumors were stratified into three molecular groups based on eight high-risk CNAs (e.g., CDKN2A/B homozygous deletion, pTERT mutation, 1p/6q/10q/14q/18q loss, 1q gain) and NF2/22q status. Associations with recurrence-free survival (RFS) were evaluated using Kaplan–Meier analysis, log-rank tests, and Cox regression models. RESULTS A total of 487 patients with intracranial meningiomas were included. The median age was 57 years (IQR, 48–67), and 332 (69.9%) were female. Group A (NF2-mutant, no high-risk CNA), Group B (NF2-wildtype, no high-risk CNA), and Group C (high-risk CNA-positive) comprised 143, 198, and 134 tumors, respectively. RFS differed significantly across groups (p &amp;lt; 0.001), with Group C exhibiting the poorest prognosis—particularly in WHO grade 1 tumors following gross total resection (GTR). In multivariable analysis, molecular group, WHO grade, and extent of resection emerged as independent predictors of recurrence. Among GTR cases, CDKN2A/B homozygous deletion, 1p/6q/10q/14q/18q losses, and 1q gain were significantly associated with shorter RFS. Oncogenic tree modeling and stratified RFS analysis suggested a stepwise accumulation of CNAs, with 22q and 1p losses as early events, and 1q gain and 10q loss as potential late-stage drivers of recurrence. CONCLUSION Molecular classification based on high-risk CNAs and NF2/22q status offers a clinically actionable framework for prognostic stratification in meningiomas. This grouping can be assessed using targeted assays and may enhance WHO grading to inform postoperative monitoring and therapeutic strategies.