Garinis George A, Patrinos George P, Spanakis Nick E, Menounos Panayiotis G
Laboratory of Reasearch, Nursing Military Academy, Athens, Greece.
Hum Genet. 2002 Aug;111(2):115-27. doi: 10.1007/s00439-002-0783-6. Epub 2002 Jul 16.
The phenotype of the cancerous cell may arise either from genetic alterations that disrupt gene function through sequence modifications (mutations) or epigenetic events that may alter the heritable state of gene expression (i.e. without changing the actual sequence of the genome). Whereas mutations in certain tumour suppressor genes are most often thought of in association with their inactivation during cancer initiation or progression, epigenetic alterations such as DNA methylation appear to be tightly linked to the sequential non-reversible events of normal tissue differentiation and organogenesis. This highlights a link between tissue differentiation and tumourigenesis with respect to the stable nature of certain epigenetic changes. In the case of tumourigenesis, both genetic and epigenetic mechanisms of altered gene expression often go hand in hand; not surprisingly, biallelic inactivation of a given tumour suppressor gene may occur via a combination of mutational and epigenetic events and is entirely consistent with the Knudson two-hit hypothesis of tumourigenesis. This review summarizes recent developments within the field of DNA methylation, highlighting its association with the transcriptional silencing of tumour suppressor genes in a variety of human cancers.
癌细胞的表型可能源于通过序列修饰（突变）破坏基因功能的基因改变，或者源于可能改变基因表达的可遗传状态（即不改变基因组的实际序列）的表观遗传事件。虽然某些肿瘤抑制基因的突变通常被认为与其在癌症发生或发展过程中的失活有关，但诸如DNA甲基化等表观遗传改变似乎与正常组织分化和器官发生的顺序不可逆事件紧密相连。这凸显了在某些表观遗传变化的稳定性方面，组织分化与肿瘤发生之间的联系。在肿瘤发生的情况下，基因表达改变的遗传和表观遗传机制往往同时出现；不足为奇的是，给定肿瘤抑制基因的双等位基因失活可能通过突变和表观遗传事件的组合发生，这与肿瘤发生的Knudson双击假说完全一致。本综述总结了DNA甲基化领域的最新进展，强调了其与多种人类癌症中肿瘤抑制基因转录沉默的关联。
