Laird Peter W
Department of Surgery and Biochemistry and Molecular Biology, University of Southern California, 90086-9176, USA.
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R65-76. doi: 10.1093/hmg/ddi113.
The field of cancer epigenetics is evolving rapidly on several fronts. Advances in our understanding of chromatin structure, histone modification, transcriptional activity and DNA methylation have resulted in an increasingly integrated view of epigenetics. In response to these insights, epigenetic therapy is expanding to include combinations of histone deacetylase inhibitors and DNA methyltransferase inhibitors. Zebularine, an orally administerable DNA methyltransferase inhibitor, has been a very promising recent addition to our arsenal of potentially useful drugs for epigenetic therapy. Aberrant DNA methylation patterns provide three powerful diagnostic applications as classification markers, sensitive detection markers, and risk assessment markers. Classification studies continue to increase in marker complexity, now incorporating microarrays, high-throughput bisulfite genomic sequencing and mass spectrometry, as the field moves to human epigenome projects. Sensitive detection technology has expanded from primarily blood-based cancer detection to include applications on a wide diversity of sample sources and is now also making inroads as a molecular risk assessment tool.
癌症表观遗传学领域正在多个方面迅速发展。我们对染色质结构、组蛋白修饰、转录活性和DNA甲基化的理解取得了进展,从而形成了对表观遗传学日益综合的观点。鉴于这些见解,表观遗传疗法正在扩展,包括组蛋白去乙酰化酶抑制剂和DNA甲基转移酶抑制剂的联合使用。泽布替尼是一种可口服的DNA甲基转移酶抑制剂,最近已成为我们用于表观遗传治疗的潜在有用药物库中非常有前景的补充药物。异常的DNA甲基化模式作为分类标记、灵敏检测标记和风险评估标记提供了三种强大的诊断应用。随着该领域向人类表观基因组计划迈进,分类研究的标记复杂性不断增加,现在纳入了微阵列、高通量亚硫酸氢盐基因组测序和质谱分析。灵敏检测技术已从主要基于血液的癌症检测扩展到包括在多种样本来源上的应用,并且现在也作为一种分子风险评估工具取得了进展。