DETECTION OF KI-RAS MUTATION IN NONNEOPLASTIC MUCOSA OF JAPANESE PATIENTS WITH COLORECTAL CANCERS

About 50% of colorectal adenocarcinoma in humans have been reported to contain mutated Ki-ras gene. To provide a better understanding for th e possible role of this mutation and to examine whether its presence c an reliably predict a risk of colorectal cancer, we have analyzed the normal appearing mucosa of patients with colorectal adenocarcinoma. Wi th an Enriched PCR procedure, we can detect mutated Ki-ras allele in t he presence of 10(3) to 10(4) normal alleles. Only by this procedure w as Ki-ras mutation detected in the non-neoplastic colonic mucosa of 9 out of 50 (18%) Japanese patients with colorectal cancer. This analysi s indicated that epithelial cells which carry mutated Ki-ras gene were 100- to 1000-fold less frequent in the non-neoplastic mucosa than at the tumor site. The presence of ras gene mutation in normal appearing mucosa points to a previous exposure which had initiated the multistag e process of colorectal carcinogenesis.