Genomic and epigenetic instability in colorectal cancer pathogenesis

被引:727
作者
Grady, William M. [4 ,5 ,6 ]
Carethers, John M. [1 ,2 ,3 ]
机构
[1] Univ Calif San Diego, Dept Med, Div Gastroenterol, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Rebecca & John Moores Comprehens Canc Ctr, La Jolla, CA 92093 USA
[3] VA San Diego Healthcare Syst, San Diego, CA USA
[4] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA
[5] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA
[6] VA Puget Sound Healthcare Syst, Seattle, WA USA
关键词
D O I
10.1053/j.gastro.2008.07.076
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:1079 / 1099
页数:21
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