Grady W M, Markowitz S
Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Curr Opin Gastroenterol. 2000 Jan;16(1):62-7. doi: 10.1097/00001574-200001000-00012.
Colon cancer results from the accumulation of genetic alterations. Genomic instability creates a permissive state in which a potential cancer cell is allowed to acquire enough mutations to become a cancer cell. Several forms of genomic instability are common in colon cancer: microsatellite instability (MSI), chromosome instability (CIN), and chromosome translocations. MSI occurs in approximately 15% of colon cancers and results from inactivation of the mutation mismatch repair (MMR) system secondary to either MMR gene mutations or hypermethylation of the hMLH1 promoter. It promotes tumorigenesis by generating mutations in target genes that possess coding microsatellite repeats, such as the transforming growth factor-beta receptor type II gene. CIN occurs in most other colon cancers and leads to a different pattern of gene alterations that culminate in tumor formation. It seems to result from mutations in genes that control mitosis, DNA damage repair, centrosome structure and function, and other fundamental processes in DNA replication. The clinical significance of genomic instability is now under investigation, and it is hoped that this research will soon yield results that have an immediate effect on the treatment of colon cancer.
结肠癌是由基因改变的积累导致的。基因组不稳定创造了一种允许状态，在这种状态下，一个潜在的癌细胞能够获得足够的突变从而变成癌细胞。几种形式的基因组不稳定在结肠癌中很常见：微卫星不稳定（MSI）、染色体不稳定（CIN）和染色体易位。MSI发生在大约15%的结肠癌中，是由于错配修复（MMR）基因突变或hMLH1启动子高甲基化继发的MMR系统失活所致。它通过在具有编码微卫星重复序列的靶基因（如转化生长因子-βⅡ型受体基因）中产生突变来促进肿瘤发生。CIN发生在大多数其他结肠癌中，并导致不同的基因改变模式，最终导致肿瘤形成。它似乎是由控制有丝分裂、DNA损伤修复、中心体结构和功能以及DNA复制中其他基本过程的基因突变引起的。基因组不稳定的临床意义目前正在研究中，希望这项研究很快能产生对结肠癌治疗有直接影响的结果。
