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- Title
Telomere length and Wnt/β-catenin pathway in adamantinomatous craniopharyngiomas.
- Authors
Soares Mota, Jose Italo; Patrício Silva-Júnior, Rui Milton; Silva Martins, Clarissa; Bueno, Ana Carolina; Wildemberg, Luiz Eduardo; da Silva Antunes, Ximene Lima; Ozaki, Jorge Guilherme Okanobo; Coeli-Lacchini, Fernanda Borchers; Garcia-Peral, Carlos; Rocha Oliveira, Antonio Edson; Carlos Santos, Antônio; Custodio Moreira, Ayrton; Machado, Helio Rubens; Volpon dos Santos, Marcelo; Colli, Leandro M.; Gadelha, Monica R.; Antonini, Sonir Roberto R.; de Castro, Margaret
- Abstract
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: 0.297-0.597 vs 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.
- Subjects
TELOMERES; RNA analysis; CRANIOPHARYNGIOMA; DNA analysis; SOMATIC mutation; DISEASE progression
- Publication
European Journal of Endocrinology, 2022, Vol 187, Issue 2, p219
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-21-1269