<Originals>Relationship of changes of p53 gene and microsatellite instability to progression of colorectal cancer

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Colorectal tumorigenesis is thought to be a multistep process in which genetic alterations accumulate and ultimately produce a neoplastic phenotype. After a colorectal carcinoma has developed, genetic alterations appear to continue to accumulate. To investigate whether changes of the p53 gene and genetic defects in the DNA-mismatch repair system were involved in the progression of colorectal carcinoma (CRC), we examined the loss of heterozygosity (LOH) on 17p and mutations in exons 5 through 8 of the p53 gene as well as replication errors (RER) at 4 microsatellite loci in DNAs from 108 CRCs of all clinical stages (20 Dukes A, 40 Dukes B, and 48 Dukes C). LOH on l7p and/or p53 mutations were detected in 93% of Dukes A carcinomas and 84% of Dukes C carcinomas, suggesting that the p53 gene is mutated and/or deleted before carcinoma develops. Approximately 30% of CRCs had an RER-positive phenotype, irrespective of the clinical stage. These results suggest that genetic instabinity is likely to play an important role in the development of subpopulation of sporadic CRCs, but not in tumor progression. In addition, we studied the relationship between p53 gene changes and genetic instability in relation of Dukes' stage, but found no significant association between genetic alterations and tumor progression. We consider that genetic defects in the DNA-mismatch repair pathaway do not necessarily promote instability of the p53 gene in CRCs.
近畿大学の論文