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癌症的表观基因组学与表观遗传治疗

Epigenomics and epigenetic therapy of cancer.

作者信息

Brown Robert, Strathdee Gordon

机构信息

Cancer Research UK Dept of Medical Oncology, Beatson Laboratories, Glasgow University, Glasgow, UK G61 1BD.

出版信息

Trends Mol Med. 2002;8(4 Suppl):S43-8. doi: 10.1016/s1471-4914(02)02314-6.

Abstract

Epigenetic inactivation of genes that are crucial for the control of normal cell growth is a hallmark of cancer cells. These epigenetic mechanisms include crosstalk between DNA methylation, histone modification and other components of chromatin higher-order structure, and lead to the regulation of gene transcription. Re-expression of genes epigenetically inactivated can result in the suppression of tumour growth or sensitization to other anticancer therapies. Small molecules that reverse epigenetic inactivation are now undergoing clinical trials in cancer patients. This, together with epigenomic analysis of chromatin alterations such as DNA methylation and histone acetylation, opens up the potential both to define epigenetic patterns of gene inactivation in tumours and to use drugs that target epigenetic silencing.

摘要

对正常细胞生长控制至关重要的基因发生表观遗传失活是癌细胞的一个标志。这些表观遗传机制包括DNA甲基化、组蛋白修饰和染色质高级结构的其他成分之间的相互作用,并导致基因转录的调控。表观遗传失活基因的重新表达可导致肿瘤生长的抑制或对其他抗癌疗法的敏感化。能够逆转表观遗传失活的小分子目前正在癌症患者中进行临床试验。这与对染色质改变(如DNA甲基化和组蛋白乙酰化)的表观基因组分析一起,为定义肿瘤中基因失活的表观遗传模式以及使用靶向表观遗传沉默的药物开辟了潜力。

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