Adamantinomatous
craniopharyngiomas (ACP) are characterized by alterations in the CTNNB1 gene while almost all
papillary craniopharyngiomas (PCP) harbor a canonical V600E mutation in the BRAF gene. Although other recurrent driver genes have not been described to date in
craniopharyngiomas, the heterogeneous
clinical course of these
tumors might be associated with the acquisition of further genomic alterations. It is well known that
telomerase reverse transcriptase (TERT) promoter (TERTp) alterations, including mutations or methylation, upregulate the expression of TERT and increase
telomerase activity, promoting
tumorigenesis. We investigated whether TERTp mutations or methylation are associated with
tumor relapse in a subset of
craniopharyngiomas. Samples from 42 patients with histologically confirmed
craniopharyngioma were retrieved. We determined TERTp, BRAF, and CTNNB1 hotspot mutations in all samples using targeted sequencing and the TERTp methylation status by methylation-specific polymerase chain reaction (PCR) in 30 samples. While BRAF V600E mutations and CTNNB1 mutations were detected in 12 (28.6%) and 21 patients (50%) in the initial
tumors and subsequent recurrences, respectively, none of the patients in our cohort, including those with multiple relapses, harbored a TERTp mutation. Furthermore, TERTp methylation was detected in 14 out of 24 cases (58.3%) with available primary samples; however, no correlation between TERTp methylation with the pathological subtype, genotype, or
tumor aggressiveness was detected. These data suggest that elevated
telomerase activity via acquisition of TERTp mutations is an infrequent pathway in the
tumorigenesis of
craniopharyngiomas, regardless of their
clinical course.