Abstract Main factors involved in carcinogenesis are associated with somatic mutations in oncogenes and tumor suppressor genes representing changes in the DNA nucleotide sequence. Epigenetic changes, such as aberrant DNA methylation, modifications of histone proteins, and chromatin remodeling, are equally important in the development of human neoplasms. From this perspective, mutations in the genes encoding key participants of epigenetic regulation are of particular interest including enzymes that methylate/demethylate DNA, enzymes that covalently attach or remove regulatory signals from histones, components of nucleosome remodeling multiprotein complexes, auxiliary proteins and cofactors of the above-mentioned molecules. This review describes both germline and somatic mutations in the key epigenetic regulators with emphasis on the latter ones in the solid human tumors, as well as considers functional consequences of these mutations on the cellular level. In addition, clinical associations of the somatic mutations in epigenetic regulators are presented, as well as DNA diagnostics of hereditary cancer syndromes due to germline mutations in the SMARC proteins and chemotherapy drugs directly affecting the altered epigenetic mechanisms for treatment of patients with solid neoplasms. The review is intended for a wide range of molecular biologists, geneticists, oncologists, and associated specialists.

中文翻译：

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实体瘤突变导致的表观遗传调控因子失活

摘要 致癌的主要因素与代表 DNA 核苷酸序列变化的癌基因和抑癌基因的体细胞突变有关。表观遗传变化，例如异常 DNA 甲基化、组蛋白修饰和染色质重塑，在人类肿瘤的发展中同样重要。从这个角度来看，编码表观遗传调控关键参与者的基因的突变特别令人感兴趣，包括甲基化/去甲基化 DNA 的酶、共价连接或去除组蛋白调控信号的酶、核小体重塑多蛋白复合物的成分、辅助蛋白和辅助因子。上面提到的分子。这篇综述描述了关键表观遗传调节因子中的种系和体细胞突变，重点是实体人类肿瘤中的后者，并考虑了这些突变在细胞水平上的功能后果。此外，还介绍了表观遗传调节因子中体细胞突变的临床关联，以及由于 SMARC 蛋白和化疗药物中的种系突变导致的遗传性癌症综合征的 DNA 诊断，直接影响治疗实体瘤患者的表观遗传机制改变。该综述面向广泛的分子生物学家、遗传学家、肿瘤学家和相关专家。介绍了表观遗传调节因子中体细胞突变的临床关联，以及由于 SMARC 蛋白和化疗药物中的种系突变导致的遗传性癌症综合征的 DNA 诊断，直接影响治疗实体瘤患者的表观遗传机制的改变。该综述面向广泛的分子生物学家、遗传学家、肿瘤学家和相关专家。介绍了表观遗传调节因子中体细胞突变的临床关联，以及由于 SMARC 蛋白和化疗药物中的种系突变导致的遗传性癌症综合征的 DNA 诊断，直接影响治疗实体瘤患者的表观遗传机制的改变。该综述面向广泛的分子生物学家、遗传学家、肿瘤学家和相关专家。