Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada;
Curr Genomics. 2008 Sep;9(6):394-408. doi: 10.2174/138920208785699580.
Both genetic and epigenetic changes contribute to development of human cancer. Oncogenomics has primarily focused on understanding the genetic basis of neoplasia, with less emphasis being placed on the role of epigenetics in tumourigenesis. Genomic alterations in cancer vary between the different types and stages, tissues and individuals. Moreover, genomic change ranges from single nucleotide mutations to gross chromosomal aneuploidy; which may or may not be associated with underlying genomic instability. Collectively, genomic alterations result in widespread deregulation of gene expression profiles and the disruption of signalling networks that control proliferation and cellular functions. In addition to changes in DNA and chromosomes, it has become evident that oncogenomic processes can be profoundly influenced by epigenetic mechanisms. DNA methylation is one of the key epigenetic factors involved in regulation of gene expression and genomic stability, and is biologically necessary for the maintenance of many cellular functions. While there has been considerable progress in understanding the impact of genetic and epigenetic mechanisms in tumourigenesis, there has been little consideration of the importance of the interplay between these two processes. In this review we summarize current understanding of the role of genetic and epigenetic alterations in human cancer. In addition we consider the associated interactions of genetic and epigenetic processes in tumour onset and progression. Furthermore, we provide a model of tumourigenesis that addresses the combined impact of both epigenetic and genetic alterations in cancer cells.
遗传和表观遗传变化共同导致人类癌症的发生。肿瘤基因组学主要侧重于了解肿瘤发生的遗传基础，而对表观遗传在肿瘤发生中的作用重视不够。癌症中的基因组改变在不同类型、不同阶段、不同组织和不同个体之间存在差异。此外，基因组改变范围从单个核苷酸突变到染色体大片段非整倍体；这些改变可能与潜在的基因组不稳定性有关，也可能没有关系。总的来说，基因组改变导致基因表达谱的广泛失调，并破坏了控制增殖和细胞功能的信号网络。除了 DNA 和染色体的改变外，人们已经明显认识到，肿瘤发生过程可以受到表观遗传机制的深刻影响。DNA 甲基化是参与基因表达和基因组稳定性调控的关键表观遗传因素之一，对于维持许多细胞功能是必不可少的。虽然人们在理解遗传和表观遗传机制在肿瘤发生中的作用方面取得了相当大的进展，但对这两个过程之间相互作用的重要性却很少考虑。在这篇综述中，我们总结了遗传和表观遗传改变在人类癌症中的作用的现有认识。此外，我们还考虑了遗传和表观遗传过程在肿瘤发生和进展中的相关相互作用。此外，我们提供了一个肿瘤发生模型，该模型考虑了癌细胞中表观遗传和遗传改变的综合影响。
