Bird A P
Institute of Cell and Molecular Biology, University of Edinburgh.
Cancer Surv. 1996;28:87-101.
There is strong evidence that DNA methylation is not a neutral bystander in carcinogenesis, but actively contributes to the process. Methylation of cytosine is known to promote mutation to thymine, and there are many examples of tumours in which tumour suppressor proteins have been rendered functionless by methylation induced mutations of this kind. There is also evidence that tumour suppressor genes can be silenced epigenetically by de novo methylation of their CpG islands in the absence of any predisposing mutation. Although the experimental results in favour of the idea are becoming highly suggestive, it is too early to consider involvement of purely epigenetic processes as proven. New data bearing on this subject will doubtless be forthcoming.
有强有力的证据表明，DNA甲基化在致癌过程中并非是一个中性旁观者，而是积极参与这一过程。已知胞嘧啶甲基化会促使其突变为胸腺嘧啶，而且在许多肿瘤实例中，肿瘤抑制蛋白因这种甲基化诱导的突变而失去功能。也有证据表明，在没有任何易感突变的情况下，肿瘤抑制基因可通过其CpG岛的从头甲基化而发生表观遗传沉默。尽管支持这一观点的实验结果越来越具有启发性，但认为纯粹的表观遗传过程参与其中已得到证实还为时过早。关于这一主题的新数据无疑将会出现。
