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

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Soares Mota, Jose Italo ; Patricio Silva-Junior, Rui Milton ; Martins, Clarissa Silva ; Bueno, Ana Carolina ; Wildemberg, Luiz Eduardo ; da Silva Antunes, Ximene Lima ; Okanobo Ozaki, Jorge Guilherme ; Coeli-Lacchini, Fernanda Borchers ; Garcia-Peral, Carlos ; Rocha Oliveira, Antonio Edson ; Santos, Antonio Carlos ; Moreira, Ayrton Custodio ; Machado, Helio Rubens ; dos Santos, Marcelo Volpon ; Colli, Leandro M. ; Gadelha, Monica R. ; Antonini, Sonir Roberto R. ; de Castro, Margaret

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 187, n. 2, p. 12-pg., 2022-08-01.

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/beta-catenin pathway and telomere biology in the pathogenesis of aCPs. (AU)

• FAPESP's process: 19/00849-2 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)
• Grantee: Rui Milton Patrício da Silva Junior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/03989-6 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)
• Grantee: Margaret de Castro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/00860-6 - Uncovering pathophysiological and molecular mechanisms involvedin tumorigenesis by platforms for next-generation sequencing (NGS)
• Grantee: Ana Carolina Bueno de Queiroz Arruda
• Support Opportunities: Scholarships in Brazil - Post-Doctoral