乳腺癌组织与血清BRCA1基因异常甲基化的临床意义  

Aberrant Hypermethylation Profile of BRCA1 in Tissue and Serum of Breast Carcinogensis

作　　者：曹清莲[1] 王作军[1,2] 冯景[1] 王耕[1] 

机构地区：[1]郧阳医学院附属太和医院,湖北十堰442000 [2]武汉大学公共卫生学院,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2010年第5期640-643,共4页Medical Journal of Wuhan University

摘　　要：目的:探讨乳腺癌BRCA1基因启动子异常甲基化状况及其在乳腺癌早期诊断中的价值。方法:用甲基化特异PCR方法对乳腺癌患者癌组织、癌旁组织及对应血浆进行BRCA1异常甲基化检测。结果:乳腺癌组织中BRCA1启动子异常甲基化检出频率为35/102(34%),血浆的检出率为32/102(32%),而癌旁组织中没有检出BRCA1异常甲基化。根据不同病理特征将35例散发性乳腺癌按组织类型、不同分级、有无淋巴结转移和年龄进行分类分析。结果显示,MSP法检测肿瘤组织与对应血浆BRCA1异常甲基化有很好的一致性(P>0.05)。102例患者的组织与血清中甲基化检出率的一致性良好(Kappa=0.765)。BRCA1基因甲基化结合病理特征表明,BRCA1基因在原位癌中甲基化检出率明显低于浸润性癌(P<0.05),有淋巴结转移相应标本BRCA1基因甲基化检出率也明显高于无淋巴结转移的标本(P<0.05),而BRCA1基因甲基化与否与肿瘤分级及年龄(绝经前后)无明显关联(P>0.05)。结论:BRCA1基因异常甲基化在乳腺癌组织与血清有相似的甲基化模式,且在乳腺癌的组织分型与转移方面有一定的鉴别诊断价值。Objective：To investigate the status of hypermethylated BRCA1 promoter in sporadic breast cancer and the value in clinical early diagnosis.Methods：The hypermethylation status of BRCA1 gene was detected in 102 sporadic breast cancer tissues,para-tumor tissue and blood plasma of normal subjects and breast cancer patients by methylation-specific PCR.Results：①Methylation rates of BRCA1 gene were 35% and 32% in cancer tissue and corresponding peripheral blood plasma respectively,while there were no hypermethylation was found in para-tumor tissues and in normal plasma controls.②Compared with primary cancer,methylation frequencies were significantly higher in invasive carcinoma（P0.005）.③Hypermethylation of BRCA1 was related with lymph node metastases.④ No significant differences in methylation frequencies were seen between pre-menopause and post-menopause or among different tumor grades （P0.05）.Conclusion：Aberrant hypermethylation of BRCA1promoter region is valuable for the determination of histological type and malignant metastases of breast cancer.

关 键 词：乳腺癌 DNA甲基化 BRCA1基因 甲基化特异PCR 

分 类 号：R737.9[医药卫生—肿瘤]