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[Impact of TERT and CDKN2A/B driver mutations on meningioma recurrence: a systematic review and meta-analysis]
G S Sergeev1, M V Nesterchuk2, V S Klimov3,4
1European Medical Center JSC, Moscow, Russia.
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.
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