癌症的表观遗传学

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Epigenetics in Cancer
Classic genetics alone cannot explain the diversity of phenotypes within a population. Nor does classic genetics explain how, despite their identical DNA sequences, monozygotic twins1 or cloned animals2 can have different phenotypes and different susceptibilities to a disease.
经典的遗传学自己不能解释人群中表现型的多样性。尽管DNA序列相同，单合子的双胞胎或者克隆的动物如何有不同的表现型和对同一疾病不同的易感性，经典的遗传学也不能解释。
The concept of epigenetics offers a partial explanation of these phenomena. First introduced by C.H. Waddington in 1939 to name \"the causal interactions between genes and their products, which bring the phenotype into being,\"3 epigenetics was later defined as heritable changes in gene expression that are not due to any alteration in the DNA sequence.4
表观遗传学的概念为这些现象提供了部分解释。1939年C.H. Waddington首先引进（此概念）以命名“基因和它们的产物间的因果交互作用，并把表现型带入生物”，表观遗传学后来定义为不归因DNA序列任何改变的基因表达的遗传学改变。

The best-known epigenetic marker is DNA methylation. The initial finding of global hypomethylation of DNA in human tumors5 was soon followed by the identification of hypermethylated tumor-suppressor genes,6,7,8,9,10,11 and then, more recently, the discovery of inactivation of microRNA (miRNA) genes by DNA methylation.12,13 These and other demonstrations of how epigenetic changes can modify gene expression have led to human epigenome projects14 and epigenetic therapies.15 Moreover, we now know that DNA methylation occurs in a complex chromatin network and is influenced by the modifications in histone structure that are commonly disrupted in cancer cells.16,17,18,19
最有名的表观遗传学标记是DNA甲基化。全球最初发现人类肿瘤中DNA的低甲基化，接着是肿瘤抑制基因高甲基化的识别，然后，最近的是，甲基化的DNA使miRNA失活的发现。这些和其他的表观遗传变化如何修饰基因表达的说明，已经引入人类基因组计划和表观遗传学的治疗。此外，我们现在知道DNA甲基化发生于一个复杂的染色质网，并被在肿瘤细胞中通常断裂的组蛋白结构的修饰所影响

Epigenetic research uses powerful techniques for the study of DNA methylation, such as sodium bisulfite modification associated with polymerase-chain-reaction procedures.20,21 Terms used in epigenetic research are defined in the Glossary.
表观遗传学的研究应用强有力的技术研究DNA甲基化，如亚硫酸氢钠与PCR程序关联。表观遗传学研究应用的术语在词汇表中有定义。
Comprehensive epigenomic techniques22 have yielded preliminary descriptions of the epigenomes of human cancer cells.23,24,25 This review summarizes new developments concerning hypermethylation of the promoter regions of tumor-suppressor genes26 and describes possible applications of epigenetics to the treatment of patients with cancer.

广泛的表观基因技术已经初步产生，以描述人类肿瘤细胞的表观基因组。这个综述概括了肿瘤抑制基因启动子区域甲基化相关的新发展，也描述了表观基因学在肿瘤患者治疗中的应用。
表观遗传学能够在经典遗传学解释不了的方面有所建树，是一种补充，更是一种超越
众所周知，人类基因组只占所有DNA序列的极少一部分，其他部分的作用是什么呢？也许表观遗传学的出现为这个困扰大家已久的问题提供了一个契机，甲基化的封闭与乙酰化的活化等修饰使许多非必要基因处于不同的状态（表达与不表达，低表达与高表达），从而使得生命出现诸多的多样性。目前的研究热点miRNA的出现更使得另一群转录控制因素浮出水面，这些来自于DNA而又不表达为蛋白质的序列可能受到DNA表观修饰更大的作用吗？期待着相关研究的进一步揭示。