Detection of Ki-ras mutation in non-neoplasticfd 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 the possible role of this mutation and to examine whether its presence can reliably predict a risk of colorectal cancer, we have analyzed the normal appearing mucosa of patients with colorectal adenocarcinoma. With an Enriched PCR procedure, we can detect mutated Ki-ras allele in the presence of 10³ to 10⁴ normal alleles. Only by this procedure was Ki-ras mutation detected in the non-neoplastic colonic mucosa of 9 out of 50 (18%) Japanese patients with colorectal cancer. This analysis 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 multistage process of colorectal carcinogenesis.