Cheung Hoi-Hung, Lee Tin-Lap, Rennert Owen M, Chan Wai-Yee
Section on Developmental Genomics, Laboratory of Clinical Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Birth Defects Res C Embryo Today. 2009 Dec;87(4):335-50. doi: 10.1002/bdrc.20163.
DNA methylation plays an important role in regulating normal development and carcinogenesis. Current understanding of the biological roles of DNA methylation is limited to its role in the regulation of gene transcription, genomic imprinting, genomic stability, and X chromosome inactivation. In the past 2 decades, a large number of changes have been identified in cancer epigenomes when compared with normals. These alterations fall into two main categories, namely, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or heterochromatin, respectively. Aberrant methylation of genes controlling the cell cycle, proliferation, apoptosis, metastasis, drug resistance, and intracellular signaling has been identified in multiple cancer types. Recent advancements in whole-genome analysis of methylome have yielded numerous differentially methylated regions, the functions of which are largely unknown. With the development of high resolution tiling microarrays and high throughput DNA sequencing, more cancer methylomes will be profiled, facilitating the identification of new candidate genes or ncRNAs that are related to oncogenesis, new prognostic markers, and the discovery of new target genes for cancer therapy.
DNA甲基化在调节正常发育和致癌过程中发挥着重要作用。目前对DNA甲基化生物学作用的理解仅限于其在基因转录调控、基因组印记、基因组稳定性和X染色体失活中的作用。在过去20年中,与正常情况相比,癌症表观基因组中已发现大量变化。这些改变主要分为两类,即肿瘤抑制基因的高甲基化和癌基因或异染色质的低甲基化。在多种癌症类型中已发现控制细胞周期、增殖、凋亡、转移、耐药性和细胞内信号传导的基因发生异常甲基化。甲基化组全基因组分析的最新进展产生了大量差异甲基化区域,其功能大多未知。随着高分辨率平铺微阵列和高通量DNA测序技术的发展,将对更多癌症甲基化组进行分析,有助于鉴定与肿瘤发生相关的新候选基因或非编码RNA、新的预后标志物以及发现癌症治疗的新靶基因。