Genomic and epigenetic instability in colorectal cancer pathogenesis.
Genomic and epigenetic instability in colorectal cancer pathogenesis.
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DOI：
10.1053/j.gastro.2008.07.076
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发表时间：
2008-10
期刊：
影响因子：
29.4
通讯作者：
Carethers JM
中科院分区：
文献类型：
--
作者：
Grady WM;Carethers JM
结直肠癌的发生是基因改变(基因突变、基因扩增等)和表观遗传改变(DNA甲基化异常、染色质修饰等)积累的结果，这些改变将结肠上皮细胞转化为结肠腺癌细胞。基因组稳定性的丧失和由此导致的基因改变是发生在肿瘤发生早期的关键分子致病步骤；它们允许获得足够数量的肿瘤抑制基因和癌基因的改变，这些基因可以转化细胞并促进肿瘤的进展。在结肠癌中发现的两种主要的基因组不稳定形式是微卫星不稳定和染色体不稳定。在确定结肠细胞染色体不稳定的原因和确定不同形式的基因组不稳定对结肠肿瘤的生物学和临床行为的影响方面已经取得了实质性的进展。除了基因组的不稳定性，表观遗传不稳定性还会导致肿瘤抑制基因的异常甲基化。确定基因组和表观基因组不稳定性在结肠癌形成中的原因和作用，有可能为结直肠癌患者提供更有效的预防策略和治疗方法。
Colorectal cancer arises as a consequence of the accumulation of genetic alterations (gene mutations, gene amplification, and so on) and epigenetic alterations (aberrant DNA methylation, chromatin modifications, and so on) that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic stability and resulting gene alterations are key molecular pathogenic steps that occur early in tumorigenesis; they permit the acquisition of a sufficient number of alterations in tumor suppressor genes and oncogenes that transform cells and promote tumor progression. Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and chromosome instability. Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more effective prevention strategies and therapeutics for patients with colorectal cancer.
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