TERT Promoter Mutations and Risk of Recurrence in Meningioma

Abstract

The World Health Organization (WHO) classification and grading system attempts to predict the clinical course of meningiomas based on morphological parameters. However, because of high interobserver variation of some criteria, more reliable prognostic markers are required. Here, we assessed the TERT promoter for mutations in the hotspot regions C228T and C250T in meningioma samples from 252 patients. Mutations were detected in 16 samples (6.4% across the cohort, 1.7%, 5.7%, and 20.0% of WHO grade I, II, and III cases, respectively). Data were analyzed by t test, Fisher's exact test, log-rank test, and Cox proportional hazard model. All statistical tests were two-sided. Within a mean follow-up time in surviving patients of 68.1 months, TERT promoter mutations were statistically significantly associated with shorter time to progression (P < .001). Median time to progression among mutant cases was 10.1 months compared with 179.0 months among wild-type cases. Our results indicate that the inclusion of molecular data (ie, analysis of TERT promoter status) into a histologically and genetically integrated classification and grading system for meningiomas increases prognostic power. Consequently, we propose to incorporate the assessment of TERT promoter status in upcoming grading schemes for meningioma.

Figure 1.

Kaplan-Meier plots of time to progression in TERT promoter mutant vs wild-type samples (A) and World Health Organization (WHO) grade I-III vs TERT mutant (B). Tables below plots indicate patients at risk at time points 0, 100, and 225 months. All statistical tests were two-sided Brier prediction plot of WHO grading vs TERT status. The reference group is the marginal Kaplan-Meier prediction model (C). mut = mutant; WHO = World Health Organization; wt = wild-type.