Integrating Methylome and Transcriptome Signatures Expands the Molecular Classification of the Pituitary Tumors.

Autor:	Silva-Júnior RMPD; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Bueno AC; Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Martins CS; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Coelli-Lacchini F; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Ozaki JGO; Department of Medical Imaging, Hematology and Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., 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, Brazil., Marrero-Gutiérrez J; Department of Medical Imaging, Hematology and Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Santos ACD; Department of Medical Imaging, Hematology and Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Garcia-Peral C; Institute of Neuroscience of Castilla y León, University of Salamanca, Salamanca 37007, Spain., Machado HR; Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Santos MVD; Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Elias PL; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Moreira AC; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., Colli LM; Department of Medical Imaging, Hematology and Oncology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, 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, Brazil., Antonini SR; Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil., de Castro M; Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, SP CEP 14049-900, Brazil.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2023 May 17; Vol. 108 (6), pp. 1452-1463.
DOI:	10.1210/clinem/dgac703
Abstrakt:	Objective: To explore pituitary tumors by methylome and transcriptome signatures in a heterogeneous ethnic population. Methods: In this retrospective cross-sectional study, clinicopathological features, methylome, and transcriptome were evaluated in pituitary tumors from 77 patients (61% women, age 12-72 years) followed due to functioning (FPT: GH-secreting n = 18, ACTH-secreting n = 14) and nonfunctioning pituitary tumors (NFPT, n = 45) at Ribeirao Preto Medical School, University of São Paulo. Results: Unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65 out of 77) revealed 3 clusters each: one enriched by FPT, one by NFPT, and a third by ACTH-secreting and NFPT. Comparison between each omics-derived clusters identified 3568 and 5994 differentially methylated and expressed genes, respectively, which were associated with each other, with tumor clinical presentation, and with 2017 and 2022 WHO classifications. UHCA considering 11 transcripts related to pituitary development/differentiation also supported 3 clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; and TBX19 in few NFPTs). Conclusion: This large heterogenic ethnic Brazilian cohort confirms that integrated methylome and transcriptome signatures classify FPT and NFPT, which are associated with clinical presentation and tumor invasiveness. Moreover, the cluster NFPT/ACTH-secreting adenomas raises interest regarding tumor heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO definition regarding the discrepancy, in rare cases, between clinical presentation and pituitary lineage markers. Finally, making our data publicly available enables further studies to validate genes/pathways involved in pituitary tumor pathogenesis and prognosis. (© The Author(s) 2022. 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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