Genetic changes in multi-step development of colorectal cancer.

We studied activated mutations of K-ras gene in three forms of colorectal tumors, i.e., 45 specimens of colorectal adenoma (CA), 10 of 'cancer in adenoma' (CIA), and 24 of colorectal cancer (CC), and in 15 of gastric cancer (GC) as controls. Chromosome aberrations were also examined in 7 specimens of CA, 3 of CIA, 8 of CC, and 7 of GC. Mutation of K-ras Codon 12 was observed in 12 (26.7%) of the 45 specimens of CA, 6 (60.0%) of the 10 specimens of CIA, 6 (25.0%) of the 24 specimens of CC, and 1 (6.7%) of the 15 specimens of GC. In CA, its frequency increased with the degree of histological atypism. In CA and CIA, its frequency increased with the increase in short diameter. The most frequent chromosome aberration was the numerical excess of chromosome 7. Numerical deficiencies of chromosomes 17 and 18 or structural abnormalities of 17p+ and 18q+ were noted in 1 specimen each of CA and CIA, and 2 of CC. Thus, aberrations of these two chromosomes were concurrent. 5q--was observed in 1 specimen each of CA and CC. These findings were not contradictory to the multi-step carcinogenesis model of the colorectum based on the hypothesis that carcinogenesis requires activation of an oncogene by mutation accompanied by defects of several genes that might normally inhibit tumorigenesis.