Epigenetic stochasticity, nuclear structure and cancer: the implications for medicine
Epigenetic stochasticity, nuclear structure and cancer: the implications for medicine
复制标题
DOI：
10.1111/joim.12224
复制
发表时间：
2014-07-01
影响因子：
11.1
通讯作者：
Feinberg, A. P.
中科院分区：
文献类型：
--
作者：
Feinberg, A. P.
这篇综述的目的是总结人类癌症的表观遗传学基础的思想演变，从最早的癌症DNA甲基化改变的研究到现代综合表观基因组时代。原发性癌症的表观遗传学研究和染色质在发育和上皮-间充质转化的实验研究的数据表明，表观遗传随机性作为癌症的驱动力的作用，达尔文选择肿瘤细胞以牺牲宿主为代价。这种增加的表观遗传随机性似乎是由与核纤层相关的DNA甲基化和染色质的大规模变化介导的。对诊断的影响包括在癌症发展前几年识别stochemical破坏的祖细胞的潜力，以及将药物靶向基因表达不稳定性的表观遗传驱动因素，而不是本身的平均效应。
The aim of this review is to summarize an evolution of thinking about the epigenetic basis of human cancer, from the earliest studies of altered DNA methylation in cancer to the modern comprehensive epigenomic era. Converging data from epigenetic studies of primary cancers and from experimental studies of chromatin in development and epithelial-mesenchymal transition suggest a role for epigenetic stochasticity as a driving force of cancer, with Darwinian selection of tumour cells at the expense of the host. This increased epigenetic stochasticity appears to be mediated by large-scale changes in DNA methylation and chromatin in domains associated with the nuclear lamina. The implications for diagnosis include the potential to identify stochastically disrupted progenitor cells years before cancer develops, and to target drugs to epigenetic drivers of gene expression instability rather than to mean effects per se.