O6.08 * COMBINED ANALYSIS OF TERT, EGFR AND IDH STATUS DEFINE DISTINCT PROGNOSTIC CLASSES OF GLIOBLASTOMA

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 the TERT promoter mutation in DNA from 395 glioblastomas and analyzed the results with their respective histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosomes 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 for TERTp-mut vs. 53.6 years for TERT promoter wild type (TERTp-wt) p < 0.0001). TERTp-mut was an independent factor of poor prognosis (OS= 13.8 vs. 18.4 months), in both IDH mutated (OS= 13.8 vs. 37.6 months, p= 0.022) and IDH wild type (IDHwt) 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 than in EGFR-amp GBM (OS= 26.6 vs. 13.3 months; p= 0.005). In the EGFR-wt group, TERTp-wt patients had a significantly better outcome (OS= 26.3 vs. 12.5 months; p< 0.0001), whereas in the EGFR-amp group, TERTp-mut patients survived longer (OS = 15.8 vs. 13.3 months; p= 0.05). Taken together, the absence of both EGFR-amp and Tertp-mut is associated with longer survival in glioblastoma patients (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.