DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features.

Autor:	Mosella MS; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA.; Department of Genetics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Sabedot TS; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA., Silva TC; Department of Genetics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Malta TM; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA., Dezem FS; Department of Genetics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Asmaro KP; Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA., Wells M; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA., Mukherjee A; Department of Pathology, Henry Ford Health System, Detroit, Michigan, USA., Poisson LM; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA.; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA., Snyder J; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA., deCarvalho AC; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA., Walbert T; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA., Aho T; Department of Radiology, Henry Ford Health System, Detroit, Michigan, USA., Kalkanis S; Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA., Elias PC; Internal Medicine Department, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Antonini SR; Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil., Rock J; Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA., Noushmehr H; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA.; Department of Genetics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Castro M; Internal Medicine Department, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Castro AV; Hermelin Brain Tumor Center, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2021 Aug 02; Vol. 23 (8), pp. 1292-1303.
DOI:	10.1093/neuonc/noab044
Abstrakt:	Background: Distinct genome-wide methylation patterns cluster pituitary neuroendocrine tumors (PitNETs) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize, and validate methylation signatures that objectively classify PitNET into clinicopathological groups. Methods: Combining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumors (Panpit cohort) and 20 nontumor specimens from the pituitary gland. We also retrieved methylome data from an independent PitNET cohort (N = 86) to validate our findings. Results: We identified three methylation clusters associated with adenohypophyseal cell lineages and functional status using an unsupervised approach. Differentially methylated probes (DMP) significantly distinguished the Panpit clusters and accurately assigned the samples of the validation cohort to their corresponding lineage and functional subtypes memberships. The DMPs were annotated in regulatory regions enriched with enhancer elements, associated with pathways and genes involved in pituitary cell identity, function, tumorigenesis, and invasiveness. Some DMPs correlated with genes with prognostic and therapeutic values in other intra- or extracranial tumors. Conclusions: We identified and validated methylation signatures, mainly annotated in enhancer regions that distinguished PitNETs by distinct adenohypophyseal cell lineages and functional status. These signatures provide the groundwork to develop an unbiased approach to classifying PitNETs according to the most recent classification recommended by the 2017 WHO and to explore their biological and clinical relevance in these tumors. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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