TERTpromoter mutations in primary and secondary WHO grade III meningioma

Purpose:TERTpromoter mutation (TERTp(Mut)) has a strong association to recurrence and has been suggested to act as a driver mutation for malignant transformation of WHO grade I and II meningiomas.TERTp(Mut)has been investigated in selected high-grade meningioma samples. The existence ofTERTp(Mut)across recurrent tumors in a population-based cohort needs to be investigated in order to identify whenTERTp(Mut)emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors.Methods:We gathered material from a consecutive single-center cohort of 40 patients with malignant meningioma (WHO grade III) treated between 2000 and 2018, including specimens from primary and secondary malignant meningiomas with the corresponding earlier benign specimens and later malignant recurrences. In total 107 tumor samples were studied by Sanger sequencing forTERTpromoter mutational status.Results:Seven of 40 patients (17.5%) harboredTERTp(Mut)thus validating the incidence ofTERTp(Mut)in previous non-population-based cohorts. In 6/7 patients, theTERTp(Mut)was present at initial surgery (WHO grade I-III) while in one patient theTERTp(Mut)was foundde novowhen the meningioma became malignant. The incidences were 2/1.000.000/year forTERTp(Mut)WHO grade III meningioma and 8/1.000.000/year forTERTp(wt)WHO grade III meningioma in our catchment area. We found a 1.7 times higher recurrence rate (CI 95% 0.65-4.44) and a 2.5 higher mortality rate per 10 person-years (CI 95% 1.01-6.19) forTERTp(Mut)compared toTERTp(wt).Conclusion:TERTp(Mut)can occur independently of malignant progression in meningioma and was most often present from the first tumor sample across recurring tumors.TERTp(Mut)in WHO grade III may represent a marker of an aggressive subset of tumors.

Automated summary

In a study of 40 patients with WHO grade III meningioma, TERTp (Mut) was found in 17.5% of cases, suggesting it may represent an aggressive subset of tumors. TERTp (Mut) can occur independently of malignant progression and is often present from the initial tumor sample through recurring tumors.