ALLELIC LOSS OF CHROMOSOME 17P, MUTATION OF THE P53 GENE, AND MICROSATELLITE INSTABILITY IN RIGHT-SIDED AND LEFT-SIDED COLORECTAL-CANCER

BACKGROUND. Epidemiologic and genetic studies suggest that cancer of t he right and left sides of the bowel arise through different mechanism s. To investigate the molecular mechanisms, allelic loss of chromosome 17p, p53 mutations, and microsatellite instability were analyzed in c olorectal cancer according to tumor site. METHODS. Using the polymeras e 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 colo rectal cancers. Allelic loss of chromosome 17p was studied by restrict ion 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 demonst rated that 63 of 108 tumors had a mutated p53 gene in exons 5, 6, 7, o r 8. When comparing the frequency of mutation in each exon based on tu mor site, the frequency of mutation in exon 8 in right-sided (2 of 18 informative cases) tumors was significantly lower than that observed i n left-sided (17 of 45 informative cases) tumors. RER(+) was observed in 43% of right-sided tumors, whereas 24% of left-sided tumors were RE R(+). Although the difference was not statistically significant, a tre nd was observed between RER(+) phenotype and tumor site. CONCLUSIONS. Our results suggest that the molecular mechanisms of colorectal carcin ogenesis may differ between right- and left-sided tumors. (C) 1996 Ame rican Cancer Society.