Multiplicative Impact of Specific Somatic Copy Number Alterations on Meningioma Recurrence Risk

Introduction: Meningiomas are the most prevalent primary intracranial tumors in adults, with clinical management traditionally guided by the World Health Organization (WHO) grading system. However, discrepancies between histological grade and clinical behavior highlight the limitations of this system. Somatic copy number alterations (SCNAs) have been implicated in meningioma pathogenesis, correlating with tumor aggressiveness and recurrence risk. Their integration into prognostic models may enhance outcomes. This study investigates the influence of SCNAs on meningioma recurrence, focusing on their patterns of mutual exclusivity and co-occurrence.

Methods: We analyzed 334 primary meningiomas, noting 23 recurrences (6.9%). Clinical data, including age, sex, WHO grade, and tumor characteristics, were collected. SCNAs and mutations were derived from whole-exome sequencing of tumor and matched blood samples. We employed univariate and multivariate Cox proportional hazards regression analyses to identify SCNAs associated with recurrence, fitting the regression model with the cumulative number of SCNAs as a factor covariate. The Kaplan-Meier estimator was utilized for visualizing survival curves.

Results: Five SCNAs were significantly associated with recurrence risk (adjusted P < 0.05): 10qLOSS, 11pLOSS, 2pLOSS, 14qLOSS, and 18qLOSS. Each SCNA independently increased recurrence risk; a single SCNA tripled this risk, while two co-occurring SCNAs increased it more than ninefold (P = 0.00003). Notably, meningiomas with four co-occurring SCNAs exhibited a greater than 22-fold increase in recurrence risk. Importantly, all identified SCNAs contributed to chromosomal instability, suggesting a synergistic effect that enhances tumor recurrence potential.

Conclusion : The accumulation and specific combinations of these five SCNAs significantly enhance the likelihood of meningioma recurrence. Although chr1pLOSS did not independently predict recurrence, it promotes chromosomal instability that facilitates the accumulation of these risk SCNAs. Our findings underscore the potential of SCNAs in predicting meningioma recurrence across all grades, contributing to improved patient management strategies.