Abstract
TERT promoter (TERTp) mutation is the most common mutation in glioblastomas. It creates a putative binding site for Ets/TCF transcription factors, enhancing telomerase expression and activity, whereas the rs2853669 variant disrupts another Ets/TCF binding. We explore here the interaction between these two alterations, tumor genomic profile and the impact on prognosis. The TERTp and rs2853669 statuses were determined and confronted with the outcome and molecular profile, i.e., loss of chromosome 10q, CDKN2A deletion, IDH mutation, EGFR amplification, MGMT promoter methylation. 651 glioblastomas were selected (sex ratio = 1.35, median age 60.4 years, median survival 13.5 months). The TERTp mutation found in 481 patients (74 %) was independent from rs2853669 genotypes. TERTp mutation, but not rs2853669 status, was associated with older age (61.4 vs. 52.8 years). rs2853669 status had no impact on overall survival (OS) either in mutated TERTp or wild-type TERTp. Neither rs2736100 (TERT, 5q15.33) nor rs192011116 (TERC, 3q26.2) status had any impact on survival or showed any association with a TERTp mutation. The TERTp mutation was associated with EGFR amplification chromosome 10q loss, CDKN2A deletion and IDH wt. EGFR amplification was associated with a better outcome in TERTp mutated GBM, and a worse outcome in TERTp WT. This study—the largest analyzing the TERTp mutation and the rs2853669 polymorphism—fails to find any prognostic impact of rs2853669. It confirms the dual prognostic impact of EGFR amplification depending on TERTp status.
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Acknowledgments
Work supported by the Fondation ARC. UN was supported by a grant from the University of Pavia and the Association pour la Recherche sur les Tumeurs Cérébrales. The research leading to these results has received funding from the program “investissements d’avenir” ANR-10-IAIHU-06. The authors are indebted to Alexandru Agachi for English Editing.
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Umberto Nencha, Amithys Rahimian and Marine Giry have contributed equally to the data presented in this paper.
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Supplementary material 1 (PPTX 129 kb) Survival curves according to the surgical procedure. Survival curves according to EGFR, chromosome 10q, CDKN2A, MGMTp methylation, IDH and TERTp mutation status. Survival curves according to upfront treatment modality in MGMT methylated and non methylated GBM
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Nencha, U., Rahimian, A., Giry, M. et al. TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas. J Neurooncol 126, 441–446 (2016). https://doi.org/10.1007/s11060-015-1999-3
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DOI: https://doi.org/10.1007/s11060-015-1999-3