散发性乳腺癌中BRCA1基因甲基化状态与其mRNA表达水平的相关研究

Study in BRCA1 gene methylation status and mRNA expression level in sporadic breast cancer

目的:探讨山东半岛地区散发性乳腺癌中BRCA1基因异常甲基化状态及其与mRNA表达的关系,进而研究其BRCA1基因异常的表观遗传学作用。方法:用甲基化特异性PCR和RT-PCR等方法研究乳腺癌组织、癌旁正常组织及乳腺良性肿瘤中BRCA1基因启动子甲基化状态及其mRNA表达水平。结果:在30例散发性乳腺癌中,BRCA1基因甲基化率为43%,BRCA1 mRNA表达下降率为33%。在13例BRCA1发生甲基化的癌组织标本中,BRCA1 mRNA的表达下降率为55%,而在17例BRCA1未发生甲基化的癌组织中,BRCA1 mRNA的表达下降率为18%。在肿瘤分级中,T3分级病人的肿瘤组织中BRCA1甲基化率(74%)和mRNA表达下降率(54%),均分别高于T1+T2分级病人肿瘤组织的BRCA1甲基化率(26%)和mRNA表达下降率(30%);有淋巴结转移病人的肿瘤组织中,BRCA1甲基化率(61%)和mRNA表达下降率(46%),均分别高于无淋巴结转移的甲基化率(17%)和mRNA表达下降率(16%)。结论:BRCA1基因表观遗传学改变是其mRNA表达下降乃至失活的重要原因,且与散发性乳腺癌的恶性程度及淋巴结转移的发生密切相关。

Objective To investigate the relationship between the abnormal methylation condition of BRCA1 gene in sporadic breast cancer and the changes in the expression level of its mRNA in the region of Shandong peninsula;study in the abnormal epigenetical role of BRCA1 gene in sporadic breast cancer.Methods To research the methylation status of BRCA1 gene promoter and the changes in the expression level of its mRNA in breast cancer tissue,corresponding adjacent normal tissue and benign breast tumor tissue with the methylation-specific PCR and RT-PCR methods.Results In 30 cases with sporadic breast cancer,the methylation rate of BRCA1 gene was 43%,and the decrease in expression rate was 33%;the expression rate dropped to 55% in 13 cases with cancerous tissue samples with BRCA1 methylation,while the rate of unmethylated cases（17 cases） was 18%.In relation to the classification of the tumor,the BRCA1 methylation rate was 74% in the tumor tissue of cases belonging to grade T3,which was higher than the total rate of 26% in grades of T1 and T2;while the mRNA expression rate of decline（54%） was also higher than the total rate of 30% in grades T1 and T2 patients.The BRCA1 methylation rate（61%） and the declination rate of mRNA expression in patients with lymph node metastasis（46%） were higher than both the corresponding rates（17% and 16%） in patients without lymph node metastasis.Conclusions The declination or inactivation of BRCA1 mRNA expression may be due to the epigenetic change in the BRCA1 gene,which is closely related to the grade of malignancy in sporadic breast cancer and the associated lymph node metastasis.