Craniopharyngiomas, including Recurrent Cases, Lack TERT Promoter Hotspot Mutations

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Shingo Fujio - , Harvard Medical School (HMS) (Autor:in)
  • Tareq A Juratli - , Klinik und Poliklinik für Neurochirurgie, Harvard Medical School (HMS), Massachusetts General Hospital (Autor:in)
  • Tomoko Takajo - , Kagoshima University (Autor:in)
  • Kazunori Arita - , Kagoshima University (Autor:in)
  • Yushi Nagano - , Kagoshima University (Autor:in)
  • Koji Yoshimoto - , Kagoshima University (Autor:in)
  • Naema Nayyar - , Harvard Medical School (HMS) (Autor:in)
  • William T Curry - , Harvard Medical School (HMS) (Autor:in)
  • Maria Martinez-Lage - , Harvard Medical School (HMS) (Autor:in)
  • Daniel P Cahill - , Harvard Medical School (HMS) (Autor:in)
  • Fred G Barker - , Harvard Medical School (HMS) (Autor:in)
  • Priscilla K Brastianos - , Harvard Medical School (HMS) (Autor:in)

Abstract

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)385-391
Seitenumfang7
FachzeitschriftNeurologia medico-chirurgica
Jahrgang61
Ausgabenummer6
PublikationsstatusVeröffentlicht - 15 Juni 2021
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC8258007
Scopus 85108386967

Schlagworte

Schlagwörter

  • Craniopharyngioma/genetics, Humans, Mutation, Neoplasm Recurrence, Local/genetics, Pituitary Neoplasms/genetics, Promoter Regions, Genetic/genetics, Telomerase/genetics