Abstract
AIMS: Microsatellite instability (MSI) was first observed in hereditary
non-polyposis colorectal carcinoma (HNPCC) and was subsequently seen
in non-familial colorectal carcinoma. The relation between MSI and
cancer associated genes in non-familial colorectal carcinomas has
yet to be evaluated. To clarify this matter, changes in cancer associated
genes were examined in non-familial colorectal carcinomas. METHODS:
Alterations in the adenomatous polyposis coli (APC), p53, and Ki-ras
genes were analysed in 24 MSI high (alterations in four to seven
of seven loci), nine MSI low (alterations in one to three of seven
loci), and 31 MSI negative non-familial carcinomas. The hMSH2 and
hMLH1 genes were also analysed in 24 MSI high carcinomas. RESULTS:
Both the frequencies and types of alterations in the APC and p53
genes in MSI high carcinomas were the same as those in MSI low and
MSI negative carcinomas; however, they were different from those
seen in HNPCC. The frequency of Ki-ras mutation was significantly
lower in the MSI high cases (two of 24; 8%) than in the others (15
of 38; 39%). Somatic mutation of hMSH2 or hMLH1 was detected in six
of 24 (25%) of the MSI high cases. CONCLUSIONS: These results suggest
that APC and p53 alterations occur irrespective of microsatellite
instability status in non-familial colorectal carcinomas, and that
Ki-ras mutation is not involved in MSI high non-familial colorectal
carcinoma. The pathogenesis of these carcinomas may differ from both
the usual adenoma-carcinoma sequence and HNPCC carcinogenesis.
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