Impact of TERT and CDKN2A/B driver mutations on meningioma recurrence: a systematic review and meta-analysis

Background. Evolution of the WHO classification for meningiomas demonstrates a shift towards integrative approach, where molecular markers are essential for risk stratification. However, their prognostic significance depending on histological grade requires further clarification. Objective. To evaluate the impact of TERT promoter mutations and CDKN2A/B deletions on meningioma recurrence, stratified by tumor grade. Material and methods. A systematic review and meta-analysis (PRISMA-P) of 17 cohort studies (n=5867) was conducted. Random-effect models and network meta-analysis were employed to assess overall survival (OS) and progression-free survival (PFS). Results. The TERT mutation significantly worsens prognosis (OS HR=2.78; PFS HR=2.63), but the effect is context-dependent. In WHO Grade 1–2 tumors, it acts as a potent driver of aggression (HR~5.00, “initiation effect”), whereas in Grade 3 its contribution diminishes (HR~1.5) amidst general genomic instability. Homozygous deletion of CDKN2A/B is confirmed as a universal marker of early recurrence (HR=3.72) with up to 5-fold risk increment. Sensitivity analysis revealed that clonal mutations (detected by Sanger sequencing) hold greater prognostic value than subclonal ones (detected by NGS). Conclusion. TERT screening is essential for WHO Grade 1 and 2 meningiomas to identify occult aggression, while CDKN2A/B assessment is a priority for Grade 3 tumors.