Epigenomic reactivation screening to identify genes silenced by DNA hypermethylation in human cancer.
Epigenomic reactivation screening to identify genes silenced by DNA hypermethylation in human cancer.
复制标题
DOI：
--
复制
发表时间：
2007-06
影响因子：
--
通讯作者：
A. Karpf
中科院分区：
文献类型：
--
作者：
A. Karpf
启动子DNA高甲基化是肿瘤抑制基因在人类癌症中失活的关键表观遗传机制。这一机制重要性的发现促使人们开发了许多方法来鉴定癌症中因DNA高甲基化而沉默的基因。这些方法中最有用的一种是表观基因组再激活筛选策略，该策略包括在体外使用DNA甲基转移酶和/或组蛋白去乙酰化酶抑制剂处理癌细胞，然后使用微阵列进行全基因表达分析，以鉴定上调的基因。当辅以微阵列分析来鉴定在原发性肿瘤中受抑制的基因时，这种方法最为有效。与直接分析癌症相关的DNA甲基化变化相比，表观基因组再激活筛选具有许多关键优势；最显著的是，它直接鉴定出表观遗传变化导致基因表达改变的基因。越来越多的研究利用表观基因组再激活筛选来发现癌症中的新型肿瘤抑制基因。本综述重点介绍了一些最新研究的结果。
Promoter DNA hypermethylation is the key epigenetic mechanism by which tumor suppressor genes are inactivated in human cancer. The discovery of the importance of this mechanism has spurred the development of a number of approaches to identify genes silenced by DNA hypermethylation in cancer. One of the most useful of these approaches is an epigenomic reactivation screening strategy that combines treatment of cancer cells in vitro with DNA methyltransferase and/or histone deacetylase inhibitors, followed by global gene expression analysis using microarrays, to identify upregulated genes. This approach is most effective when complemented by microarray analyses to identify genes repressed in primary tumors. Epigenomic reactivation screening has a number of key advantages over direct analysis of cancer-associated DNA methylation changes; most notably, it directly identifies genes in which epigenetic changes lead to altered gene expression. An increasing number of studies have utilized epigenomic reactivation screening to discover novel tumor suppressor genes in cancer. The results of some of the most recent studies are highlighted in this review.