Distinct epigenetic changes in the stromal cells of breast cancers
Distinct epigenetic changes in the stromal cells of breast cancers
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DOI：
10.1038/ng1596
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发表时间：
2005-08-01
期刊：
影响因子：
30.8
通讯作者：
Polyak, K
中科院分区：
文献类型：
--
作者：
Hu, M;Yao, J;Polyak, K
越来越多的证据表明，细胞微环境的变化有助于肿瘤的发生，但这些改变的分子基础还没有很好地理解。尽管肿瘤中肿瘤细胞的表观遗传修饰与肿瘤发生密切相关（1），但尚不清楚表观遗传修饰是否发生在非肿瘤基质细胞中。为了以公正和全基因组的方式解决这个问题，我们开发了一种新的方法，甲基化特异性数字核型分析，并将其应用于上皮和肌上皮细胞，正常乳腺组织的基质成纤维细胞，原位和浸润性乳腺癌。我们的分析表明，不同的表观遗传学改变发生在所有三种细胞类型在乳腺肿瘤发生在肿瘤阶段和细胞类型特异性的方式，表明表观遗传学的变化有一个在乳腺癌中的异常细胞微环境的维护中的作用。
Increasing evidence suggests that changes in the cellular microenvironment contribute to tumorigenesis, but the molecular basis of these alterations is not well understood. Although epigenetic modifications of the neoplastic cells in tumors have been firmly implicated in tumorigenesis(1), it is not known whether epigenetic modifications occur in the non-neoplastic stromal cells. To address this question in an unbiased and genome-wide manner, we developed a new method, methylation-specific digital karyotyping, and applied it to epithelial and myoepithelial cells, stromal fibroblasts from normal breast tissue, and in situ and invasive breast carcinomas. Our analyses showed that distinct epigenetic alterations occur in all three cell types during breast tumorigenesis in a tumor stage- and cell type-specific manner, suggesting that epigenetic changes have a role in the maintenance of the abnormal cellular microenvironment in breast cancer.