Prognostic significance of telomerase reverse transcriptase promoter mutations in high grade meningiomas

Abstract

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic value of telomerase reverse transcriptase mutations in Colombian patients with grade II and III meningioma. Materials and methods: Multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grade II and III meningioma, recruited between 2011 and 2018, managed with systemic therapy (sunitinib, everolimus +/- octreotide and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was performed by PCR. Results: 40 patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), the most frequent variants being C228T and C250T, 87.5% and 14.3%, respectively. These were more frequent among patients with anaplastic meningiomas (p = 0.18), with >2 recurrences (p = 0.04), and in lesions of the parasagittal region and anterior fossa (p = 0.05). Subjects characterized as having punctual alterations were more frequently exposed to the sequence E → Su → Bev (p = 0.06). OS after initiation of medical treatment was 23.7 months (95% CI 13.1-34.2) and 43.4 months (95% CI 37.5-49.3; p = 0.0001) between subjects with and without mutations, respectively. In multivariate analysis, it was shown that only the number of recurrences and the presence of telomerase reverse transcriptase mutations negatively affected OS. Conclusions: Telomerase reverse transcriptase allows identifying high-risk patients and could be useful to select the best sequence of medical treatment.