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

Autor: Jose Italo Soares Mota, Rui Milton Patrício Silva-Júnior, Clarissa Silva Martins, Ana Carolina Bueno, Luiz Eduardo Wildemberg, Ximene Lima da Silva Antunes, Jorge Guilherme Okanobo Ozaki, Fernanda Borchers Coeli-Lacchini, Carlos Garcia-Peral, Antonio Edson Rocha Oliveira, Antônio Carlos Santos, Ayrton Custodio Moreira, Helio Rubens Machado, Marcelo Volpon dos Santos, Leandro M Colli, Monica R Gadelha, Sonir Roberto R Antonini, Margaret de Castro
Rok vydání: 2022
Předmět:
Zdroj: European Journal of Endocrinology. 187:219-230
ISSN: 1479-683X
0804-4643
DOI: 10.1530/eje-21-1269
Popis: 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.
Databáze: OpenAIRE
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