Different methylation and MicroRNA expression pattern in male and female familial breast cancer

Abstract

Epigenetic regulation, has been very scarcely explored in familial breast cancer (BC). In the present study RASSF1A and RAR beta promoter methylation and miR17, miR21, miR 124, and let-7a expression were investigated to highlight possible differences of epigenetic regulation between male and female familial BC, also in comparison with sporadic BC. These epigenetic alterations were studied in 56 familial BC patients (27 males and 29 females) and in 16 female sporadic cases. RASSF1A resulted more frequently methylated in men than women (76% vs. 28%, respectively, P = 0.0001), while miR17 and let-7a expression frequency was higher in women than in men (miR17: 66% in women vs. 41% in men, P < 0.05; let-7a: 45% in women vs. 15% in men, P = 0.015). RASSF1A methylation affected 27.6% of familial BC while 83% of familial cases showed high expression of the gene (P = 0.025); on the contrary, only 17% of familial BC presented RAR beta methylation and 55% of familial cases overexpressed this gene (P = 0.005). Moreover, miR17, miR21, and let-7a resulted significantly overexpressed in familial compared to sporadic BC. RASSF1A overexpression (86% vs. 65%, P = 0.13) and RAR beta overexpression (57% vs. 32%, P = 0.11) were higher in BRCA1/2 carriers even if not statistical significance was reached. BRCA mutation carriers also demonstrated significant overexpression of: miR17 (93% vs. 35%, P = 0.0001), let-7a (64% vs. 16%, P = 0.002), and of miR21 (100% vs. 65%, P = 0.008). In conclusion, the present data suggest the involvement of RASSF1A in familial male BC, while miR17 and let-7a seem to be implied in familial female BC.

Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer

“…Interestingly, we found that lower levels of miR-124 are associated with advanced TNM stage (stage I + II vs. stage III + IV, P = 0.0007) and positive lymph node metastasis, suggesting that a low expression of miR-124 is associated with breast cancer progression. Recently, miR-124 was reported to be subject to epigenetic regulation in various tumors, including breast cancer [17,31,32,34], which in turn may explain the downregulation of miR-124 in breast cancer. Taken together, these results suggest that miR-124 expression is frequently reduced in breast cancer, which may be responsible for the tumorigenesis and progression of breast cancer.…”

Influence of sex differences on microRNA gene regulation in disease

“…al. presented a significant correlation between miR17 and let-7a frequency and regulation in familial breast cancer in women compared to men [87]. Langevin et.…”

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

“…The need for more refined therapeutic treatments for male breast cancer (MBC) is evidenced by a steady stream of publications highlighting gender-specific differences using IHC (1-5), genetics (6)(7)(8)(9)(10)(11), and more recently, epigenetics (12)(13)(14)(15). Of note, although MBC is similar histologically to female breast cancer (FBC), with the same panel of biomarkers used to guide treatment and prognosis, more rigorous interrogation of the underlying genetics shows heterogeneity in MBC as recognized in FBC where molecular profiling has identified different subgroups that correlate with varying clinical outcomes.…”