Investigation of GHSR methylation levels in thymomas from patients with Myasthenia Gravis

Fabio Coppedè; Andrea Stoccoro; Vanessa Nicolì; Roberta Gallo; Anna De Rosa; Melania Guida; Michelangelo Maestri; Marco Lucchi; Roberta Ricciardi; Lucia Migliore

doi:10.1016/j.gene.2020.144774

Investigation of GHSR methylation levels in thymomas from patients with Myasthenia Gravis

Gene. 2020 Aug 20:752:144774. doi: 10.1016/j.gene.2020.144774. Epub 2020 May 19.

Authors

Affiliations

¹ Department of Translational Research and of New Surgical and Medical Technologies, Lab. of Medical Genetics, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy. Electronic address: fabio.coppede@med.unipi.it.
² Department of Translational Research and of New Surgical and Medical Technologies, Lab. of Medical Genetics, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy.
³ Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy.
⁴ Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, Pisa University Hospital, Pisa, Italy; Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
⁵ Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Pisa, Italy; Division of Thoracic Surgery, Cardiothoracic and Vascular Surgery Department, Pisa University Hospital, Pisa, Italy.
⁶ Department of Translational Research and of New Surgical and Medical Technologies, Lab. of Medical Genetics, University of Pisa, Medical School, Via Roma 55, 56126 Pisa, Italy; Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy.

PMID: 32442579
DOI: 10.1016/j.gene.2020.144774

Abstract

Background: Hypermethylation of the growth hormone secretagogue receptor gene (GHSR) is increasingly observed in human cancers, suggesting that it could represent a pan-cancer biomarker of clinical interest. However, little is still known concerning GHSR methylation levels in thymic epithelial tumors, and particularly in thymomas from patients with Myasthenia Gravis (TAMG).

Material and methods: In the present study we collected DNA samples from circulating lymphocytes and surgically resected tumor tissues of 65 TAMG patients, and from the adjacent healthy thymic tissue available from 43 of them. We then investigated GHSR methylation levels in the collected tissues searching for correlation with the clinical characteristics of the samples.

Results: GHSR hypermethylation was observed in 18 thymoma samples (28%) compared to the healthy thymic tissues (P < 1 × 10^-4), and those samples were particularly enriched in advanced disease stages than stage I (94% were in stage II or higher). GHSR was demethylated in the remaining 47 thymomas, as well as in all the investigated healthy thymic samples and in circulating lymphocytes.

Conclusions: GHSR hypermethylation is not a pan-cancer marker or an early event in TAMG, but occurs in almost 1/4 of them and mainly from stage II onward. Subsequent studies are required to clarify the molecular pathways leading to GHSR hypermethylation in TAMG tissues and their relevance to disease progression.

Keywords: Cancer; DNA methylation; Epigenetics; GHSR; Myasthenia gravis; Thymoma.

MeSH terms

Adult
Aged
DNA Methylation / genetics
Female
Humans
Lymphocytes / pathology
Male
Middle Aged
Myasthenia Gravis / genetics*
Myasthenia Gravis / metabolism
Neoplasms, Glandular and Epithelial / genetics
Receptors, Ghrelin / genetics*
Receptors, Ghrelin / metabolism
Thymoma / genetics
Thymus Neoplasms / genetics

Substances

Receptors, Ghrelin

Supplementary concepts

Thymic epithelial tumor