Allelic loss of chromosome 17p, mutation of the p53 gene, and microsatellite instability in right- and left-sided colorectal cancer

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Abstract
BACKGROUND Epidemiologic and genetic studies suggest that cancer of the right and left sides of the bowel arise through different mechanisms. To investigate the molecular mechanisms, allelic loss of chromosome 17p, p53 mutations, and microsatellite instability were analyzed in colorectal cancer according to tumor site. METHODS Using the polymerase chain reaction and single strand conformation polymorphism (PCR‐SSCP) method, mutations within exons 5–8 of the p53 gene were examined in 108 colorectal cancers including 30 right‐sided and 78 left‐sided colorectal cancers. Allelic loss of chromosome 17p was studied by restriction fragment length polymorphism analysis, and genetic instability was examined for replication error (RER) at three microsatellite loci on chromosomes 2p, 17p, and 17q. RESULTS Allelic loss was observed in 61% (14 of 23 informative cases) of right‐sided tumors and in 60% (26 of 43 informative cases) of left‐sided tumors. PCR‐SSCP analysis demonstrated that 63 of 108 tumors had a mutated p53 gene in exons 5, 6, 7, or 8. When comparing the frequency of mutation in each exon based on tumor site, the frequency of mutation in exon 8 in right‐sided (2 of 18 informative cases) tumors was significantly lower than that observed in left‐sided (17 of 45 informative cases) tumors. RER(+) was observed in 43% of right‐sided tumors, whereas 24% of left‐sided tumors were RER(+). Although the difference was not statistically significant, a trend was observed between RER(+) phenotype and tumor site. CONCLUSIONS Our results suggest that the molecular mechanisms of colorectal carcinogenesis may differ between right‐ and left‐sided tumors. Cancer 1996;77:1688‐93.