TERT promoter mutations in meningiomas: associations with clinicopathological features and insights into spatial and temporal heterogeneity in a 165-case cohort.

Background: Although most meningiomas are benign, some behave aggressively despite low grade. We investigated the prognostic significance of TERT promoter (TERTp) mutations regarding clinicopathological features, heterogeneity, and outcomes.

Methods: A total of 165 meningiomas diagnosed between 2007 and 2019 were retrospectively re-evaluated according to the 2021 WHO CNS classification. TERTp mutations were assessed by real-time PCR targeting C228T and C250T. Spatial heterogeneity was examined by microdissecting rhabdoid and non-rhabdoid areas, and temporal heterogeneity by comparing initial and recurrent tumors. Associations between TERTp mutation status, clinicopathological parameters, and survival were analyzed.

Results: TERTp mutations were detected in 6.7 % (n = 11). Mutation-positive tumors had higher mitotic counts (p = 0.007), but TERTp mutation status was not an independent predictor of recurrence or survival (p > 0.05). Spatial heterogeneity was observed, with rhabdoid areas mutation-negative and non-rhabdoid areas mutation-positive. Temporal heterogeneity was observed in tumors initially negative but positive at relapse. Extent of resection, spinal location, and age were independent prognostic factors.

Conclusion: TERTp mutation was associated with mitotic activity but did not independently predict outcome. However, the small number of mutation-positive cases (n = 11; three recurrences) and grade 3 tumors (n = 3), and absence of broader molecular profiling (e.g., BAP1, NF2, CDKN2A/B, methylation, CNVs) limit generalizability and statistical power, warranting cautious interpretation. Spatial heterogeneity underscores the need for representative sampling, while temporal heterogeneity suggests a potential role of TERTp mutations in tumor evolution. These findings highlight the potential importance of spatial and temporal heterogeneity of TERTp mutations in meningiomas, underscoring the need for integrated molecular profiling in future studies.