RESUMO
BACKGROUND: Telomerase reverse transcriptase promoter (pTERT) mutation is a dominant altered telomere maintenance mechanism in primary glioblastomas (GBMs). OBJECTIVE: The aim of this study was to correlate pTERT mutations with clinico-histological features and other molecular markers (p53 protein-expression, ATRX protein-expression, IDH mutations, EGFR gene amplification and MGMT methylation) in adult GBMs. MATERIALS AND METHODS: Evaluated for histological patterns, p53 and ATRX protein expression by immunohistochemistry (IHC), IDH mutations by IHC followed by sequencing in IHC negative cases, EGFR gene amplification by fluorescence in situ hybridization, MGMT promoter methylation by methylation-specific PCR and pTERT mutation by sequencing. RESULTS: A total of 155 adult supratentorial GBMs [age-range 20-80 years] formed study cohort. 15.6% were IDH1R132 mutated, none were IDH2R172 mutated and 27% were EGFR amplified. 43% were MGMT methylated and were more common with IDH-mutation (mIDH) than EGFR amplification. 90% of mIDH (but no EGFR amplified) cases showed ATRX-loss. 43.5% were pTERT mutated (C228T was the commonest type) and were mutually exclusive with ATRX-loss. 14% of mIDH and 42% of EGFR amplified cases showed pTERT mutation, the latter was more commonly pMGMT unmethylated (63.6%). CONCLUSIONS: 43.5% of the GBMs showed pTERT mutation (C228T was commonest; 72%). pTERT mutations were mutually exclusive with ATRX protein loss, more commonly associated with IDH wild type and EGFR amplified GBMs.
