Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens
Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens
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DOI：
10.1093/carcin/21.9.1761
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发表时间：
2000-09-01
期刊：
影响因子：
4.7
通讯作者：
Futscher, BW
中科院分区：
文献类型：
--
作者：
Rice, JC;Ozcelik, H;Futscher, BW
BRCA1的功能失活是参与乳腺癌发病的重要机制。突变通常是家族性乳腺癌中BRCA1失活的原因，但不是散发性乳腺癌患者中BRCA1水平降低的原因。为了确定BRCA1启动子的异常胞嘧啶甲基化是否与人类乳腺癌中BRCA1基因表达下降有关，我们使用高分辨率亚硫酸酯序列分析分析了21例已知BRCA1表达水平的腋窝结阴性乳腺癌患者BRCA1启动子的胞嘧啶甲基化状态。21例患者标本中有3例检测到BRCA1启动子胞嘧啶甲基化异常，这3例标本也表达了最低水平的BRCA1。本分析结果表明，BRCA1启动子胞嘧啶甲基化异常与人类乳腺癌中BRCA1表达水平下降直接相关，并提示表观遗传沉默可能是散发性乳腺癌中BRCA1转录失活的一种机制。
Functional inactivation of BRCA1 is an important mechanism involved in breast cancer pathogenesis. Mutation is often responsible for BRCA1 inactivation in familial breast cancer, but is not responsible for the decreased levels of BRCA1 seen in a subset of sporadic breast cancer patients. To determine if aberrant cytosine methylation of the BRCA1 promoter is associated with decreased BRCA1 gene expression in human breast cancer, high resolution bisulfite sequence analysis was used to analyze the cytosine methylation status of the BRCA1 promoter in 21 axillary node negative breast cancer patients with known levels of BRCA1 expression. Aberrant cytosine methylation of the BRCA1 promoter was detected in three of 21 patient specimens, These three specimens also expressed the lowest levels of BRCA1. Results from this analysis show that aberrant cytosine methylation of the BRCA1 promoter is directly correlated with decreased levels of BRCA1 expression in human breast cancer, and suggest that epigenetic silencing may be one mechanism of transcriptional inactivation of BRCA1 in sporadic mammary carcinogenesis.