Artikel
Prognostic value of TERT promoter mutation in aggressive meningiomas
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Autoren
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Annamaria Biczok
- Klinikum Grosshadern, Klinikum Grosshadern, Neurochirurgische Klinik und Poliklinik, München, Deutschland
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Theo Kraus
- Klinikum Grosshadern, Klinikum Grosshadern, Abteilung für Neuropathologie und Prionenforschung, München, Deutschland
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Bogdana Suchorska
- Klinikum Grosshadern, Klinikum Grosshadern, Neurochirurgische Klinik und Poliklinik, München, Deutschland
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Nicole Angela Terpolilli
- Klinikum Grosshadern, Klinikum Grosshadern, Neurochirurgische Klinik und Poliklinik, München, Deutschland
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Christian Schichor
- Klinikum der Ludwig-Maximilians-Universität München, Neurosurgical Clinic, Campus Grosshadern, München, Deutschland
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Jörg-Christian Tonn
- Klinikum Grosshadern, Klinikum Grosshadern, Neurochirurgische Klinik und Poliklinik, München, Deutschland
| Veröffentlicht: | 9. Juni 2017 |
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Gliederung
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Objective: Transcriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene occur at high frequency in various types of solid tumors. In atypical and anaplastic meningiomas, however incidence and significance of TERT mutations are still largely unkown. The aim of the present study was to investigate the frequency of TERT promoter mutations in a cohort of atypical and anaplastic meningiomas and to define prognostic significance for progression free survival and overall survival.
Methods: Patients undergoing surgical resection of WHO grade II and WHO grade III meningiomas from 01/2001 to 12/2014 were included into the analysis. TERT analysis for C228T and C250T mutations in the TERT promoter region was performed using PCR method. Patients were stratified into 2 groups (TERT mutation vs. TERT wild type). Univariate and multivariate analysis was conducted using molecular and histological factors as well as surgical features.
Results: During the follow up time of 38.5 months, 88 patients with atypical (n=73) and anaplastic meningiomas (n=15) were included in the study. TERT promoter region C228T or C250T mutation was found to be mutated in 4 WHO grade II (5.5%) and 2 WHO grade III (13.3%) meningiomas. Presence of TERT mutations were equally distributed between genders (present in 5.7% female and 7.5% of male patients), age did not differ between the subgroups. Meningiomas harboring TERT mutation did not show a strong predilection for any location, with an equally distribution between convexity (n=3) and skull base location (n=3). Presence of a TERT mutation was associated with shorter progression free survival than TERT wild type (median PFS 12.5 months vs 26 months). In the multivariate analysis, TERT promoter mutation had a strong independent prognostic value on overall survival (median OS 26 months vs 40 months) in aggressive meningiomas (p=0.009 HR=4.872).
Conclusion: Presence of TERT promoter mutation variant C228T and C250T was associated with shorter PFS and OS in aggressive meningiomas. TERT mutation status should be considered a clinically relevant prognostic factor in meningiomas WHO grade II and III identifying patients at higher risk for recurrence and progression.
