Holčáková Jitka
Klin Onkol. 2018 Winter;31(Suppl 2):41-45. doi: 10.14735/amko20182S41.
Research in the last decade has confirmed the importance of epigenetic processes for the onset, development, and treatment of cancer. Next generation sequencing has allowed the inspection and mapping of the human epigenome and its monitoring for changes during carcinogenesis, which has revealed direct links between epigenetic abnormalities and mutations in genes that control DNA methylation and packing and those that function in chromatin dynamics and metabolism. Epigenetic changes that occur in the early stages of tumor progression thus represent promising candidates for diagnostic and prognostic markers, and epigenetic processes are suitable targets for the development of new therapeutic strategies. There are two contrasting views on how aberrant DNA methylation contributes to the development of cancer. The first view assumes that normal cells undergo transformation due to driver mutations and subsequent de novo methylation and DNA demethylation, resulting in global changes in gene expression. The second view considers changes in DNA methylation to be a consequence of cell aging, for example, and that the acquired changes increase the sensitivity of DNA to mutations and oncogenic transformation.
The aim of the review article is to briefly summarize the role of abnormal DNA methylation in the development of cancer, and to present an alternative theory that considers the role of aberrant DNA methylation patterns in cancer from a new and unconventional perspective. Key words: DNA methylation - polycomb-group proteins - CpG islands The work was supported by the project MEYS - NPS I - LO1413. The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 27. 8. 2018.
过去十年的研究证实了表观遗传过程在癌症的发生、发展和治疗中的重要性。新一代测序技术使得对人类表观基因组的检测和图谱绘制以及对其在致癌过程中变化的监测成为可能，这揭示了表观遗传异常与控制DNA甲基化和包装的基因以及在染色质动力学和代谢中起作用的基因的突变之间的直接联系。因此，肿瘤进展早期发生的表观遗传变化是诊断和预后标志物的有希望的候选者，并且表观遗传过程是开发新治疗策略的合适靶点。关于异常DNA甲基化如何促进癌症发展存在两种截然不同的观点。第一种观点认为正常细胞由于驱动突变以及随后的从头甲基化和DNA去甲基化而发生转化，导致基因表达的全局变化。第二种观点认为DNA甲基化的变化是细胞衰老的结果，例如，获得的变化增加了DNA对突变和致癌转化的敏感性。
这篇综述文章的目的是简要总结异常DNA甲基化在癌症发展中的作用，并从一个新的和非常规的角度提出一种考虑异常DNA甲基化模式在癌症中作用的替代理论。关键词：DNA甲基化 - 多梳蛋白家族 - CpG岛 本研究得到了MEYS - NPS I - LO1413项目的支持。作者声明她在研究中使用的药物、产品或服务方面没有潜在的利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。接受日期：2018年8月27日。
