Division of Cancer Cell Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Trends Genet. 2021 Nov;37(11):1012-1027. doi: 10.1016/j.tig.2021.05.002. Epub 2021 Jun 10.
DNA methylation is a chemical modification that defines cell type and lineage through the control of gene expression and genome stability. Disruption of DNA methylation control mechanisms causes a variety of diseases, including cancer. Cancer cells are characterized by aberrant DNA methylation (i.e., genome-wide hypomethylation and site-specific hypermethylation), mainly targeting CpG islands in gene expression regulatory elements. In particular, the early findings that a variety of tumor suppressor genes (TSGs) are targets of DNA hypermethylation in cancer led to the proposal of a model in which aberrant DNA methylation promotes cellular oncogenesis through TSGs silencing. However, recent genome-wide analyses have revealed that this classical model needs to be reconsidered. In this review, we will discuss the molecular mechanisms of DNA methylation abnormalities in cancer as well as their therapeutic potential.
DNA 甲基化是一种化学修饰，通过控制基因表达和基因组稳定性来定义细胞类型和谱系。DNA 甲基化控制机制的破坏会导致多种疾病，包括癌症。癌细胞的特征是异常的 DNA 甲基化（即全基因组低甲基化和特定位点高甲基化），主要针对基因表达调控元件中的 CpG 岛。特别是，早期发现多种肿瘤抑制基因（TSGs）是癌症中 DNA 高甲基化的靶标，这导致了一种模型的提出，即异常的 DNA 甲基化通过 TSGs 的沉默促进细胞癌发生。然而，最近的全基因组分析表明，这一经典模型需要重新考虑。在这篇综述中，我们将讨论癌症中 DNA 甲基化异常的分子机制及其治疗潜力。
