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| Autor(es): Mostrar menos - |
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
Número total de Autores: 18
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| Tipo de documento: | Artigo Científico |
| Fonte: | EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 187, n. 2, p. 12-pg., 2022-08-01. |
| Resumo | |
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) | |
| Processo FAPESP: | 19/00849-2 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-generation sequencing) |
| Beneficiário: | Rui Milton Patrício da Silva Junior |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 14/03989-6 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-Generation Sequencing) |
| Beneficiário: | Margaret de Castro |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 19/00860-6 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-generation sequencing). |
| Beneficiário: | Ana Carolina Bueno de Queiroz Arruda |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |