Department of Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK.
Department of Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK; Gastrointestinal Translational Research Unit, Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
Eur J Surg Oncol. 2019 May;45(5):736-746. doi: 10.1016/j.ejso.2019.02.005. Epub 2019 Feb 5.
Cancer is initiated through both genetic and epigenetic alterations. The end-effect of such changes to the DNA machinery is a set of uncontrolled mechanisms of cell division, invasion and, eventually, metastasis. Epigenetic changes are now increasingly appreciated as an essential driver to the cancer phenotype. The epigenetic regulation of cancer is complex and not yet fully understood, but application of epigenetics to clinical practice and in cancer research has the potential to improve cancer care. Epigenetics changes do not cause changes in the DNA base-pairs (and, hence, does not alter the genetic code per se) but rather occur through methylation of DNA, by histone modifications, and, through changes to chromatin structure to alter genetic expression. Epigenetic regulators are characterized as writers, readers or erasers by their mechanisms of action. The human epigenome is influenced from cradle to grave, with internal and external life-time exposure influencing the epigenetic marks that may act as modifiers or drivers of carcinogenesis. Preventive and public health strategies may follow from better understanding of the life-time influence of the epigenome. Epigenetics may be used to define risk, to investigate mechanisms of carcinogenesis, to identify biomarkers, and to identify novel therapeutic options. Epigenetic alterations are found across many solid cancers and are increasingly making clinical impact to cancer management. Novel epigenetic drugs may be used for a more tailored and specific response to treatment of cancers. We present a primer on epigenetics for surgical oncologists with examples from colorectal cancer, breast cancer, pancreatic cancer and hepatocellular carcinoma.
癌症是通过遗传和表观遗传改变引发的。这些 DNA 机制的变化的最终结果是一系列不受控制的细胞分裂、侵袭和最终转移机制。表观遗传变化现在被越来越多地认为是癌症表型的一个重要驱动因素。癌症的表观遗传调控非常复杂，尚未完全理解，但将表观遗传学应用于临床实践和癌症研究有可能改善癌症治疗。表观遗传变化不会导致 DNA 碱基对发生变化（因此，不会改变遗传密码本身），而是通过 DNA 的甲基化、组蛋白修饰以及通过改变染色质结构来改变基因表达而发生。表观遗传调节剂通过其作用机制被描述为写入器、读取器或擦除器。人类表观基因组受终生影响，内部和外部的终生暴露会影响可能作为致癌作用修饰物或驱动物的表观遗传标记。更好地了解表观基因组的终生影响可能会产生预防和公共卫生策略。表观遗传学可用于定义风险、研究致癌机制、识别生物标志物和确定新的治疗选择。表观遗传改变在许多实体瘤中都存在，并越来越对癌症管理产生临床影响。新型表观遗传药物可用于更有针对性和更特异性地治疗癌症。我们为外科肿瘤学家提供了一个关于表观遗传学的入门知识，其中包括结直肠癌、乳腺癌、胰腺癌和肝细胞癌的例子。
