Department of Urology, Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Carcinogenesis. 2010 Jan;31(1):27-36. doi: 10.1093/carcin/bgp220. Epub 2009 Sep 13.
Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. The initiation and progression of cancer, traditionally seen as a genetic disease, is now realized to involve epigenetic abnormalities along with genetic alterations. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer including DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. The reversible nature of epigenetic aberrations has led to the emergence of the promising field of epigenetic therapy, which is already making progress with the recent FDA approval of three epigenetic drugs for cancer treatment. In this review, we discuss the current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies.
表观遗传机制对于哺乳动物正常发育和组织特异性基因表达模式的维持至关重要。表观遗传过程的破坏可导致基因功能改变和恶性细胞转化。表观基因组的全局变化是癌症的一个标志。癌症的发生和发展,传统上被视为一种遗传疾病,现在已经意识到涉及遗传改变以及表观遗传异常。癌症表观遗传学这个快速发展领域的最新进展表明,癌症中表观遗传机制的每个组成部分都经历了广泛的重编程,包括 DNA 甲基化、组蛋白修饰、核小体定位和非编码 RNA,特别是 microRNA 的表达。表观遗传异常的可逆性导致了表观遗传治疗这一有前途领域的出现,最近 FDA 批准了三种用于癌症治疗的表观遗传药物,这一领域已经取得了进展。在这篇综述中,我们讨论了与正常细胞相比,癌症中发生的表观遗传景观改变,这些改变在癌症的起始和进展中的作用,包括癌症干细胞模型,以及将这些知识应用于设计更有效的治疗策略的潜力。