实体瘤中的DNA甲基化:功能与检测方法
DNA Methylation in Solid Tumors: Functions and Methods of Detection.
作者信息
Martisova Andrea, Holcakova Jitka, Izadi Nasim, Sebuyoya Ravery, Hrstka Roman, Bartosik Martin
机构信息
Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic.
出版信息
Int J Mol Sci. 2021 Apr 19;22(8):4247. doi: 10.3390/ijms22084247.
DNA methylation, i.e., addition of methyl group to 5'-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.
DNA甲基化,即向CpG二核苷酸中胞嘧啶残基的5'-碳位添加甲基基团,是一种调节基因表达的重要表观遗传修饰,因而与许多细胞过程相关。DNA甲基化失调与包括癌症在内的多种疾病的发生密切相关。在此,我们综述DNA甲基化如何影响致癌过程,并列举经常出现异常DNA甲基化的实体瘤实例。我们解释基于以下方面在单基因和全基因组水平上进行DNA甲基化分析所开发方法的原理:(i)亚硫酸氢钠转化,(ii)甲基化敏感限制性内切酶,以及(iii)5-甲基胞嘧啶(5mC)与甲基结合蛋白或抗5mC抗体的相互作用。除了标准方法,我们还描述了应用于DNA甲基化分析的新一代测序技术的最新进展,以及作为其更廉价、更快速替代方案的生物传感器的发展。最重要的是,我们不仅强调每种方法的优点,还强调其缺点和挑战。