AUTHOR=Foschini Maria P. , Morandi Luca , Sanchez Alejandro M. , Santoro Angela , Mulè Antonino , Zannoni Gian Franco , Varga Zsuzsanna , Moskovszky Linda , Cucchi Maria C. , Moelans Cathy B. , Giove Gianluca , van Diest Paul J. , Masetti Riccardo 

TITLE=Methylation Profile of X-Chromosome–Related Genes in Male Breast Cancer

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00784

DOI=10.3389/fonc.2020.00784

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> Androgen receptor (AR) has been described to play a prominent role in male breast cancer (MBC). It maps on chromosome X, and recent reports indicate that X-chromosome polysomy is frequent in MBC. Since the response to anti-androgen therapy may depend on AR polysomy and on its overexpression similarly to prostate cancer, the aim of the present study was to investigate the DNA methylation level of <italic>AR</italic> and its coregulators, especially those mapped on the X-chromosome, that may influence the activity of AR in MBC.</p><p><bold>Methods:</bold> The DNA methylation level of <italic>AR, MAGEA2, MAGEA11, MAGEC1, MAGEC2, FLNA, HDAC6</italic>, and <italic>UXT</italic>, mapped on the X-chromosome, was evaluated by quantitative bisulfite-NGS. Bioinformatic analysis was performed in a Galaxy Project environment using BWA-METH, MethylDackel, and Methylation Plotter tools. The study population consisted of MBC (41 cases) compared with gynecomastia (17 cases).</p><p><bold>Results:</bold><italic>MAGEA</italic> family members, especially <italic>MAGEA2, MAGEA11, MAGEC</italic>, and <italic>UXT</italic> and <italic>HDAC6</italic> showed hypomethylation of several CpGs, reaching statistical significance by the Kruskal–Wallis test (<italic>p</italic> &lt; 0.01) in MBC when compared to gynecomastia. <italic>AR</italic> showed almost no methylation at all.</p><p><bold>Conclusions:</bold> Our study demonstrated for the first time that <italic>MAGEA</italic> family members mapped on the X-chromosome and coregulators of AR are hypomethylated in MBC. This may lead to their overexpression, enhancing AR activity.</p>