Telomere length and Wnt/β-catenin pathway in adamantinomatous craniopharyngiomas

Eur J Endocrinol. 2022 Jun 20;187(2):219-230. doi: 10.1530/EJE-21-1269.


Objectives: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations.

Design: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions.

Methods: Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths.

Results: Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597vs 0.607, IQR: 0.445-0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs.

Conclusions: ctnnb1: mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/β-catenin pathway and telomere biology in the pathogenesis of aCPs.

MeSH terms

  • Adolescent
  • Child
  • Craniopharyngioma* / genetics
  • Cross-Sectional Studies
  • Humans
  • Mutation
  • Retrospective Studies
  • Telomere* / ultrastructure
  • Wnt Signaling Pathway
  • beta Catenin* / genetics


  • CTNNB1 protein, human
  • beta Catenin