Jones Peter A
Department of Urology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90089-9181, USA.
Semin Hematol. 2005 Jul;42(3 Suppl 2):S3-8. doi: 10.1053/j.seminhematol.2005.05.001.
Epigenetic mechanisms including DNA and histone modifications result in silencing of genes without changing the coding sequence of the gene. Even though these events are heritable, they are potentially reversible, thus opening up opportunities for therapeutic intervention. The importance of epigenetic changes in human cancer is only now being recognized in the medical community. A series of discoveries over the last four decades has thrust epigenetics into the forefront of new drug discoveries. Three systems--DNA methylation, RNA-associated silencing, and histone modification--are used to initiate and sustain epigenetic silencing. Current knowledge suggests that agents that intervene in this process by "turning back on" silenced genes may represent a significant advancement in treating many forms of cancer. In addition, changed patterns of methylation can be detected with a high degree of sensitivity thus providing clinicians with prognostic information.
包括DNA和组蛋白修饰在内的表观遗传机制会导致基因沉默，而不改变基因的编码序列。尽管这些事件是可遗传的，但它们可能是可逆的，从而为治疗干预提供了机会。表观遗传变化在人类癌症中的重要性直到现在才在医学界得到认可。过去四十年来的一系列发现将表观遗传学推向了新药发现的前沿。DNA甲基化、RNA相关沉默和组蛋白修饰这三种系统被用于启动和维持表观遗传沉默。目前的知识表明，通过“重新开启”沉默基因来干预这一过程的药物可能代表着在治疗多种癌症方面的重大进展。此外，可以高度灵敏地检测到甲基化模式的变化，从而为临床医生提供预后信息。
