Epigenetic Control of Adamantinomatous Craniopharyngiomas.

Autor:	Marrero-Gutiérrez J; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Bueno AC; Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Martins CS; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Coeli-Lacchini FB; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Silva-Júnior RMP; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Marques Gonçalves GH; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Ozaki JGO; Department of Medical Imaging, Hematology and Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., de Almeida E Silva DC; Department of Computation and Mathematics Biology, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, 14040-901, Brazil., Wildemberg LE; Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil., da Silva Antunes XL; Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil., Dos Santos AC; Department of Medical Imaging, Hematology and Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Machado HR; Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Santos MV; Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Moreira AC; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., Gadelha MR; Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil., Vêncio RZN; Department of Computation and Mathematics Biology, Faculty of Philosophy, Sciences and Letters at Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, 14040-901, Brazil., Antonini SRR; Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil., de Castro M; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP, 14049-900, Brazil.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Sep 16; Vol. 109 (10), pp. e1867-e1880.
DOI:	10.1210/clinem/dgae006
Abstrakt:	Introduction: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. Objective: To identify methylation signatures in ACPs regarding clinical presentation and outcome. Methods: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multidimensional scaling. Statistical associations between clusters and clinical features were achieved using the Fisher test and global biological process interpretations were aided by Gene Ontology enrichment analyses. Results: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = .0006), hypomethylated in CpG island, non-CpG Island sites, and globally (P < .001), and associated with greater tumor size (24.1 vs 9.5 cm3, P = .04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell adhesion, cytoskeleton organization, and cytokine binding, and cell type-specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. Conclusion: Two clusters of patients with ACP were consistently revealed by unsupervised machine learning methods, with one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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