Inactivation of tumor suppressor genes - Choice between genetic and epigenetic routes
Inactivation of tumor suppressor genes - Choice between genetic and epigenetic routes
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DOI：
10.4161/cc.4.1.1361
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发表时间：
2005-01-01
期刊：
影响因子：
4.3
通讯作者：
Baylin, SB
中科院分区：
文献类型：
--
作者：
Chen, WY;Baylin, SB
肿瘤抑制基因的失活可以通过表观遗传或遗传机制发生。在肿瘤发生过程中选择这种基因失活途径的原因尚未阐明，也没有明确的基因在癌症进化中的确切作用，这些基因仅受表观遗传介导的功能丧失的影响。在这里，我们讨论了一个小鼠模型，在该模型中，Hic1基因的破坏可以显著影响强大的肿瘤抑制基因p53的破坏，从而决定恶性肿瘤的发病率、谱和毒力。此外，Hic1在肿瘤中失活的机制可以从表观遗传模式切换到遗传模式，这取决于Hic1和P53敲除基因在小鼠11号染色体上的定位。本文讨论了这种模型的价值以及该发现对于选择表观遗传和遗传决定的癌症基因功能丧失的意义。
Inactivation of tumor suppressor genes can occur via epigenetic or genetic mechanisms. The reasons underlying this choice of gene inactivation routes during tumorigenesis have not been clarified, nor have the precise roles in cancer evolution for genes which are solely affected by epigenetically mediated loss of function. Here we discuss a mouse model in which the disruption of Hic1, a gene solely involved with epigenetic silencing in human cancer, can markedly influence the disruption of the powerful tumor suppressor gene, p53, in determining malignant tumor incidence, spectrum and virulence. Furthermore, the mechanism for inactivation of Hic1 in tumors produced can be switched from an epigenetic to a genetic mode depending on how the Hic1 and p53 knockouts are localized on mouse chromosome 11. The value of such a model and the implications of the findings for choice of epigenetically versus genetically determined loss of gene function in cancer are discussed.