Methylation profiles of the BRCA1 promoter in hereditary and sporadic breast cancer among Han Chinese
Methylation profiles of the BRCA1 promoter in hereditary and sporadic breast cancer among Han Chinese
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中国汉族遗传性和散发性乳腺癌中 BRCA1 启动子的甲基化谱
DOI：
10.1007/s12032-011-0100-0
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发表时间：
2012-09-01
期刊：
影响因子：
3.4
通讯作者：
Yang, Yanmei
中科院分区：
文献类型：
--
作者：
Pang, Da;Zhao, Yashuang;Yang, Yanmei
乳腺癌的发展是一个多步骤的过程，与宿主基因表达模式的复杂变化有关，包括肿瘤抑制基因的失活和癌基因的激活。重要的是，遗传易感性在癌症易感性中起着重要作用。然而，BRCA1基因突变仅在少数遗传性乳腺癌中发现，这表明可能存在其他新的机制导致BRCA1基因失活。研究表明，基因组DNA的异常甲基化在癌变过程中起着重要作用。本研究的目的是研究DNA甲基化是否可能是BRCA1失活的另一种机制，作为基因组的表观遗传修饰，以及遗传性乳腺癌是否具有与散发性乳腺癌不同的BRCA1甲基化表型模式。通过对72例具有遗传易感性但没有BRCA1突变的患者和30例散发性乳腺癌对照者的外周血细胞进行亚硫酸盐测序，评估了BRCA1启动子区域CpG岛甲基化的模式。遗传易感性患者的总体甲基化水平显著低于散发性对照组。然而，与对照组相比，具有遗传易感性的患者对- 518位点的甲基化易感性明显更高。这些结果提示散发性和遗传性乳腺癌外周血DNA中可能存在不同的BRCA1启动子甲基化水平和模式。这些发现可能有助于遗传性乳腺癌的早期诊断。
The development of breast cancer is a multistep process associated with complex changes in host gene expression patterns including inactivation of tumor suppressor genes and activation of oncogenes. Critically, hereditary predisposition plays a significant role in cancer susceptibility. However, mutation of the BRCA1 gene is found only in the minority of hereditary breast cancer, which indicates that there might be alternative, novel mechanisms contributing to inactivation of the BRCA1 gene. Studies have shown that aberrant methylation of genomic DNA plays an important role in carcinogenesis. The aim of this study was to investigate whether DNA methylation may be an alternative mechanism for the inactivation of BRCA1 as an epigenetic modification of the genome and whether hereditary breast cancer has a different BRCA1 methylation phenotype pattern than sporadic breast cancer. The pattern of CpG island methylation within the promoter region of BRCA1 was assessed by bisulfite sequencing DNA from peripheral blood cells of 72 patients with hereditary predisposition but without BRCA1 mutations and 30 sporadic breast cancer controls. The overall methylation level in patients with hereditary predisposition was significantly lower than that in the sporadic control group. However, patients with hereditary predisposition showed a significantly higher methylation susceptibility for the sites −518 when compared to controls. These results suggest that there might be different BRCA1 promoter methylation levels and patterns in sporadic and hereditary breast cancer in peripheral blood DNA. These findings may facilitate the early diagnosis of hereditary breast cancer.