The chromosomal instability pathway in colon cancer.
The chromosomal instability pathway in colon cancer.
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DOI：
10.1053/j.gastro.2009.12.065
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发表时间：
2010-06
期刊：
影响因子：
29.4
通讯作者：
Chung DC
中科院分区：
文献类型：
--
作者：
Pino MS;Chung DC
基因组不稳定性的获得是肿瘤发展中的一个重要特征，并且在结直肠癌发病机制中至少存在3种不同的途径：染色体不稳定性（CIN）、微卫星不稳定性（MSI）和CpG岛甲基化表型（CIMP）途径。大多数结直肠癌病例通过CIN途径产生，其特征在于染色体数目的广泛不平衡（非整倍性）和杂合性丢失（洛）。它可能是由于染色体分离、端粒稳定性和DNA损伤反应的缺陷引起的，尽管CIN的全部基因仍没有完全描述。与CIN肿瘤中观察到的核型异常相结合的是特定肿瘤抑制基因和癌基因中一组特征性突变的积累，这些突变激活了对结直肠癌起始和进展至关重要的途径。CIN是否为这些突变的积累创造了适当的环境，或者反之亦然，仍然是一个挑衅性和未回答的问题。这篇综述的目的是提供一个更新的观点，导致CIN的机制和在这一途径中获得的关键突变。
The acquisition of genomic instability is a crucial feature in tumor development and there are at least 3 distinct pathways in colorectal cancer pathogenesis: the chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP) pathways. Most cases of colorectal cancer arise through the CIN pathway, which is characterized by widespread imbalances in chromosome number (aneuploidy) and loss of heterozygosity (LOH). It can result from defects in chromosomal segregation, telomere stability, and the DNA damage response, although the full complement of genes underlying CIN remains incompletely described. Coupled with the karyotypic abnormalities observed in CIN tumors are the accumulation of a characteristic set of mutations in specific tumor suppressor genes and oncogenes that activate pathways critical for colorectal cancer initiation and progression. Whether CIN creates the appropriate milieu for the accumulation of these mutations or vice versa remains a provocative and unanswered question. The goal of this review is to provide an updated perspective on the mechanisms that lead to CIN and the key mutations that are acquired in this pathway.
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