Li Hsin Pai, Leu Yu Wei, Chang Yu Sun
Graduate Institute of Basic Medical Sciences, Chang Gung University, Kwei-shan, Taoyuan, Taiwan.
Cell Res. 2005 Apr;15(4):262-71. doi: 10.1038/sj.cr.7290295.
Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding of specific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is a prevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increased activity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players in regulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing and the signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus 40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection of epigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigenetic changes should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection, prognosis, and therapy of cancer.
由于对特定表观遗传途径的认识不断加深以及检测技术的迅速发展,人类癌症表观遗传学成为一个新兴的研究方向。异常的启动子高甲基化是人类癌症中普遍存在的现象。由于DNA甲基转移酶(DNMTs)活性增加或失调,肿瘤抑制基因常常发生高甲基化。越来越多的证据还表明,病毒基因是调节DNA甲基化的关键因素之一。在本综述中,我们将重点关注高甲基化和肿瘤抑制基因沉默以及相关的信号通路,特别是在与乙型肝炎病毒、猿猴病毒40(SV40)和爱泼斯坦-巴尔病毒密切相关的癌症中。此外,我们将讨论目前用于全基因组检测表观遗传调控靶点的技术,这些技术可用于系统的DNA高甲基化分析。表观遗传变化的研究应能提供癌症基因谱的整体视图,表观遗传标记可用于癌症的早期检测、预后评估和治疗。