Molecular Genetics Laboratory - NCRC Giovanni Paolo II, Bari, Italy.
J Cell Physiol. 2013 Jun;228(6):1264-9. doi: 10.1002/jcp.24281.
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.
表观遗传调控在家族性乳腺癌（BC）中研究甚少。本研究旨在探讨 RASSF1A 和 RARβ启动子甲基化以及 miR17、miR21、miR124 和 let-7a 的表达，以突出家族性 BC 中男性和女性之间可能存在的表观遗传调控差异，并与散发性 BC 进行比较。在 56 例家族性 BC 患者（27 例男性和 29 例女性）和 16 例女性散发性病例中研究了这些表观遗传改变。结果显示，RASSF1A 在男性中的甲基化频率高于女性（分别为 76%和 28%，P=0.0001），而 miR17 和 let-7a 的表达频率在女性中高于男性（miR17：女性为 66%，男性为 41%，P<0.05；let-7a：女性为 45%，男性为 15%，P=0.015）。RASSF1A 甲基化影响了 27.6%的家族性 BC，而 83%的家族性病例表现出该基因的高表达（P=0.025）；相反，只有 17%的家族性 BC 出现 RARβ甲基化，而 55%的家族性病例过度表达该基因（P=0.005）。此外，miR17、miR21 和 let-7a 在家族性 BC 中的表达明显高于散发性 BC。与散发性 BC 相比，RASSF1A 过表达（86%对 65%，P=0.13）和 RARβ过表达（57%对 32%，P=0.11）在 BRCA1/2 携带者中更高，尽管未达到统计学意义。BRCA 突变携带者也表现出 miR17（93%对 35%，P=0.0001）、let-7a（64%对 16%，P=0.002）和 miR21（100%对 65%，P=0.008）的显著过表达。总之，本研究数据提示 RASSF1A 参与家族性男性 BC，而 miR17 和 let-7a 似乎与家族性女性 BC 有关。
