Research Papers:

Gene-specific methylation profiles in BRCA-mutation positive and BRCA-mutation negative male breast cancers

Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Domenico Palli and Laura Ottini _

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Oncotarget. 2018; 9:19783-19792. https://doi.org/10.18632/oncotarget.24856

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Piera Rizzolo1, Valentina Silvestri1, Virginia Valentini1, Veronica Zelli1, Ines Zanna2, Giovanna Masala2, Simonetta Bianchi3, Domenico Palli2 and Laura Ottini1

1Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy

2Cancer Risk Factors and Lifestyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPRO), Florence, Italy

3Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

Correspondence to:

Laura Ottini, email: [email protected]

Keywords: male breast cancer; promoter methylation; BRCA1/2 mutations; clinical-pathologic characteristics; pyrosequencing

Abbreviations: MBC: Male breast cancer; FBC: female breast cancer; G: tumor grade; ER: estrogen receptor; PR: progesterone receptor

Received: December 23, 2017     Accepted: February 27, 2018     Published: April 13, 2018


Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC.

In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs.

We examined 69 MBCs, paired blood samples, and 15 normal tissues for promoter methylation of hTERT, ESR1, RASSF1, AR, MYC and WNT1 genes.

MBCs showed higher gene promoter methylation levels compared to paired blood and normal breast samples. Significantly higher RASSF1 methylation levels were observed in association with BRCA1/2 mutations, HER2 expression and high tumor grade. Significantly higher AR methylation levels were observed in BRCA1/2 wild-type cases and higher WNT1 methylation levels in PR negative cases.

Overall, our results indicate that alterations in gene methylation profiles are common in MBC and that methylation pattern of tumor-associated genes may allow for the identification of MBC molecular subgroups, that could have implications in clinical management of MBC patients.

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