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

• Published in: European journal of endocrinology
• Main Authors: Mota, Jose Italo Soares, Silva-Júnior, Rui Milton Patricio, Martins, Clarissa Silva, Bueno, Ana Carolina, Wildemberg, Luiz Eduardo, Antunes, Ximene Lima da Silva, Ozaki, Jorge Guilherme Okanobo, Coeli-Lacchini, Fernanda Borchers, Garcia-Peral, Carlos, Oliveira, Antonio Edson Rocha, Santos, Antônio Carlos, Moreira, Ayrton Custodio, Machado, Helio Rubens, Dos Santos, Marcelo Volpon, Colli, Leandro M, Gadelha, Monica R, Antonini, Sonir Roberto R, de Castro, Margaret
• Format: Journal Article
• Language: English
• Published: England 01.05.2022
• ISSN: 1479-683X

To evaluate how telomeres length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Retrospective cross-sectional study enrolling 42 aCP patients from two tertiary institutions. Clinicopathological features were retrieved from 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. 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 telomere and CTNNB1-mutated aCPs. 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.