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Published on: August 25, 2021
TERT Promoter Mutations and Risk of Recurrence in Meningioma
Felix Sahm1, Daniel Schrimpf1, Adriana Olar1
1Affiliations of authors:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg , Heidelberg , Germany (FS, DS, CK, DR, JB, AK, DC, SS, AvD); Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg , Germany (FS, DS, CK, DR, AK, DC, AvD); Department of Pathology (AO), Department of Genomic Medicine (QW), Department of Radiation Oncology (QW, EPS), and Department of Bioinformatics and Computational Biology (QW), The University of Texas MD Anderson Cancer Center , Houston, TX ; Department of Radiation Oncology (SA, JD) and Department of Neurosurgery (MSc, TU, CHM), University Hospital Heidelberg , Heidelberg , Germany ; Department of Neuropathology, Charité Medical University , Berlin , Germany (AK); Department of Pathology, University Hospital Nürnberg , Nürnberg , Germany (AFO): Department of Neurosurgery, Medical Faculty of the Ruprecht-Karls-University of Heidelberg , Mannheim , Germany (SB); Department of Neuropathology, Institute of Pathology and Neuropathology, University Tübingen , Tübingen , Germany (JS); Department of Neuropathology, University of Bonn , Bonn , Germany (AB); Department of Neurosurgery (BB) and Institute of Neuropathology (WP), University Hospital Münster , Münster , Germany (BB); Department of Neurosurgery, University Hospital Bonn , Bonn , Germany (KG, MSi); Department of Neurosurgery, University Hospital Würzburg , Würzburg , Germany (AFK); Department of Neurosurgery, University Hospital Hamburg , Hamburg , Germany (KL); Department of Neuropathology, Otto von Guericke University Magdeburg , Magdeburg , Germany (CM); Institute of Pathology, Saarland University , Homburg, Saarland , Germany (YJK); Department of Neurosurgery, Saarland University , Homburg , Germany (RK); MacFeeters-Hamilton Brain Tumour Centre, Princess Margaret Cancer Center , Toronto, Ontario , Canada (KDA); Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg , Germany (TH).
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.
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