Published by Bioscientifica Ltd. Printed in Great Britain © 2022 European Society of Endocrinology https://eje.bioscientifca.com https://doi.org/10.1530/EJE-21-1269 European Journal of Endocrinology 187:2 219–230 J I S Mota, R M P Silva-Júnior and others Telomeres and β-catenin in craniopharyngiomas Telomere length and Wnt/ β-catenin pathway in adamantinomatous craniopharyngiomas Jose Italo Soares Mota 1,* , Rui Milton Patrício Silva-Júnior 1,*,† , Clarissa Silva Martins 1,‡ , Ana Carolina Bueno 2 , Luiz Eduardo Wildemberg 3 , Ximene Lima da Silva Antunes 3 , Jorge Guilherme Okanobo Ozaki 1,§ , Fernanda Borchers Coeli-Lacchini 1 , Carlos Garcia-Peral 4 , Antonio Edson Rocha Oliveira 1 , Antônio Carlos Santos 6 , Ayrton Custodio Moreira 1 , Helio Rubens Machado 5 , Marcelo Volpon dos Santos 5 , Leandro M Colli 6 , Monica R Gadelha 3 , Sonir Roberto R Antonini 2 and Margaret de Castro 1 1 Department of Internal Medicine of Ribeirao Preto Medical School, 2 Department of Pediatrics of Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil, 3 Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 4 Institute of Neuroscience of Castilla y León, University of Salamanca, Salamanca, Spain, 5 Department of Surgery and Anatomy of Ribeirao Preto Medical School, and 6 Department of Medical Imaging, Hematology and Oncology of Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil *( J I S Mota and R M P Silva-Júnior contributed equally to this work) † (R M P Silva-Júnior is now at Institute of Neuroscience of Castilla y León, University of Salamanca, Salamanca, Spain) ‡ (C S Martins is now at Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Brazil) § (J G O Ozaki is now at Sonimed Medicina Diagnóstica, Campo Grande, Brazil) 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 diferentially 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 identifed a total of 387 diferentially 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. Correspondence should be addressed to M de Castro Email castrom@fmrp.usp.br Original Research European Journal of Endocrinology (2022) 187, 219–230 Downloaded from https://academic.oup.com/ejendo/article/187/2/219/6972097 by guest on 10 January 2023