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

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 mutation-positive and -negative MBCs. We examined 69 MBCs, paired blood samples, and 15 normal tissues for promoter methylation of and genes. MBCs showed higher gene promoter methylation levels compared to paired blood and normal breast samples. Significantly higher methylation levels were observed in association with mutations, HER2 expression and high tumor grade. Significantly higher methylation levels were observed in wild-type cases and higher 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.