Analysis of DNA replication error and other genetic altherations in colorectal tumor.

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Recently, The defect of DNA mismatch repair system which is originally reported to be the cause of hereditary non-polyposis colorectal cancer (HNPCC), has been known to be involved in carcinogenesis in many sporadic cancers, such as colon, stomach or endometrial cancers. In order to know the significance of this disorder in sporadic colorectal neoplasms, DNA replication error (RER) and as the possible target of RER,the mutation of TGF beta receptor type II gene (RII), K-ras and p53 were examined using PCR-based analysis or immunohistochemistry.RER was detected in 15-20% of moderately or well differentiated adenocarcinomas. On the contrary, RER was detected in 21 out of 45 cases (46.7%) with poorly differentiated adenocarcinomas and the mutation in 10 adenine repeats of RII gene was detected in 11 out of 21 RER (+) cases and in none of RER (-) cases. In the cases with poorly differentiated adenocarcinomas, the mutation of K-ras (codon 12 and/or 13) was detected in 5 out of 22 cases (22%) and positive staining for p53 immunohistochemistry was detected in 19 out of 43 cases (44.2%). There was no correlation between RER and the mutation of K-ras or p53.These results suggested that the DNA replication error might be involved in carcinogenesis of poorly differentiated adenocarcinoma of colorectum and TGF beta receptor type II gene is the most probable candidate as a target gene for this disorder.