NF2基因甲基化及其mRNA表达与乳腺癌发病的关系(英文)

Methylation and the mRNA Expression of NF2 and their association with the Morbidity of Breast Cancer

目的:探讨乳腺癌中NF2基因启动子甲基化状态及其mRNA水平与乳腺癌发病的关系。方法:应用甲基化特异性聚合酶链反应(MSP)和逆转录-聚合酶链反应(RT-PCR)技术,检测47例乳腺癌组织及相应的癌旁组织和15例乳腺良性病变组织,分析NF2基因的甲基化与某些临床参数及mRNA表达的关系。结果:NF2基因启动子区在乳腺癌、癌旁和乳腺良性病变组织中的甲基化频率分别为57.4%(27/47)、23.4%(23/47)和0%(0/15),且乳腺癌组明显高于其余两组(P<0.05)。NF2基因发生甲基化与发病年龄、组织分型、转移和组织分级无相关性。乳腺癌组NF2基因mRNA的相对表达量(0.16±0.11)明显低于相应的癌旁组(0.27±0.14)及乳腺良性病变组(0.64±0.17()P<0.05)。NF2基因启动子区甲基化频率与其mRNA表达呈负相关(Spearman’sr=-0.314,P<0.05)。结论:NF2基因发生甲基化与乳腺癌的发生密切相关,NF2mRNA表达与NF2基因启动子高甲基化呈负相关。

Objective:To investigate the frequency of promoter hypermethylation,the expression of neurofibromatosis type 2(NF2)gene and the association with breast cancers.Methods:Methylation-specific PCR was employed to detect methylation of NF2 in the 47 breast cancer tissues,peficaneerous tissues,and 15 benign breast lesions tissues.The mRNA expression of NF2 was determined by reverse transcription PCR in the aforesaid tissues.The relationship between methylation and mRNA expression of NF2 was analyzed.Results:The frequencies of NF2 promoter methylation were 57.4%(27/47),23.4(23/47)and 0%(0/15)in breast cancer tissues,peficaneerous and benign breast lesions tissues,respectively.NF2 methylation in breast cancer tissues increased significantly compared with the other two groups(P＜0.05).No correlation was found between the methylation of NF2 and clinical features including age of onset,histological typing,lymphnode metastasis,and histological grade(P＞0.05).The expression of NF2 in breast cancer tissues(0.16±0.11)and peficaneerous tissues(0.27±0.14)was significantly lower compared with benign breast lesions tissues(0.64±0.17)(P＜0.05).Methylation of NF2 was correlated negatively with NF2 expression in breast cancer tissues.(Spearman's r=-0.314,P＜0.05).Conclusions:The aberrant promoter methylation of NF2 gene is a frequent molecular pathological event in breast cancer.NF2 mRNA expression is down regulated when the promoter is hypermethylated.