Abstract 2234: Combined analysis of TERT, EGFR and IDH status define distinct prognostic classes of GBM

Abstract

Abstract Background. The importance of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently strengthened by the frequent occurrence of TERT promoter mutations in glioblastomas. Methods. We sequenced TERT promoter mutation in 395 glioblastomas DNA and confronted the results with histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosome 9 and 10, TP53 mutation), and overall survival (OS). Results. TERT promoter mutations (TERTp-mut) were found in 299/395 glioblastomas (75.7%) and were associated with an older age (median 59.6 vs. 53.6 years p<0.0001). TERTp-mut was an independent factor of poor prognosis (OS= 13.8 months vs. 18.4 months), in both IDH mutated (OS= 13.8 months vs. 37.6., p= 0.022) and IDH wild type (IDH-wt) GBM (OS= 13.7 vs. 17.5 months, p= 0.006). TERTp-mut was associated with IDH-wt and EGFR amplification (EGFR-amp) status. In TERTp-wt group, OS was twice longer in EGFR wt compared to EGFR-amp GBM (OS= 26.6 months vs. 13.3 months; p= 0.005). In the EGFR-wt group, TERTp-wt patients had a much better outcome (OS= 26.3 vs. 12.5 months; p< 0.0001), whereas in the EGFR-amp group, TERTp-mut patients did better (OS = 15.8 vs. 13.3 months; p= 0.05). Taken together the absence of both EGFR-amp and Tertp-mut is associated with better survival (26.5 months for IDH-wt, 36.7 months for IDH-mut patients). Conclusions. The analysis of TERT promoter mutations, in combination with EGFR amplification and IDH mutation status, refines the prognostic classification of GBM. Citation Format: Marianne Labussiere, Blandine Boisselier, Karima Mokhtari, Anais Rahimian, Olivier Saulnier, Yannick Marie, Marc Sanson. Combined analysis of TERT, EGFR and IDH status define distinct prognostic classes of GBM. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2234. doi:10.1158/1538-7445.AM2014-2234