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

Frontiers in Oncology

Gianluca Giove¹  Maria P. Foschini¹  Cathy B. Moelans²  Paul J. van Diest²  Alejandro M. Sanchez³  Riccardo Masetti³  Luca Morandi⁴  Linda Moskovszky⁵  Zsuzsanna Varga⁵  Angela Santoro⁶  Gian Franco Zannoni⁶  Antonino Mulè⁶  Maria C. Cucchi⁷ 

[1] Anatomic Pathology Section “M. Malpighi”, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy;Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands;Dipartimento Scienze della Salute della donna e del Bambino e di Sanità Pubblica, Multidisciplinary Breast Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;Functional MR Unit, Department of Biomedical and Neuromotor Sciences, IRCCS Istituto delle Scienze Neurologiche di Bologna, University of Bologna, Bologna, Italy;Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland;Pathology Unit, Dipartimento Scienze della Salute della donna e del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;Unit of Breast Surgery, Department of Oncology, Bellaria Hospital, AUSL Bologna, Bologna, Italy;

关键词: male breast cancer;    androgen receptor;    MAGE family;    DNA methylation;    X-chromosome;    FLNA;   

DOI  :  10.3389/fonc.2020.00784

来源: DOAJ

【 摘 要 】

Background: 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 AR and its coregulators, especially those mapped on the X-chromosome, that may influence the activity of AR in MBC.Methods: The DNA methylation level of AR, MAGEA2, MAGEA11, MAGEC1, MAGEC2, FLNA, HDAC6, and UXT, 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).Results:MAGEA family members, especially MAGEA2, MAGEA11, MAGEC, and UXT and HDAC6 showed hypomethylation of several CpGs, reaching statistical significance by the Kruskal–Wallis test (p < 0.01) in MBC when compared to gynecomastia. AR showed almost no methylation at all.Conclusions: Our study demonstrated for the first time that MAGEA family members mapped on the X-chromosome and coregulators of AR are hypomethylated in MBC. This may lead to their overexpression, enhancing AR activity.

【 授权许可】

Unknown