K-RAS ACTIVATION IN GASTRIC EPITHELIAL TUMORS IN JAPANESE

Point mutation in codons 12, 13 and 61 of the K-ras oncogene in gastric epithelial tumors were investigated by polymerase chain reaction from sections of formalin-fixed, paraffin-embedded tissue followed by dot-blot hybridization with mutation-specific oligonucleotide probes. Point mutations were found specifically in four of 20 tumors of intestinal histological subtype; GGT to GAT in three cases and to GTT in one case, all in codon 12 of K-ras. These mutations were also confirmed by direct sequencing. In contrast, none of 11 diffuse-type tumors showed K-ras point mutations. While K-ras point mutations may not be frequent events in gastric tumorigenesis, the similarity of the intestinal-type gastric tumors and colorectal tumors for K-ras point mutations as well as the association of mutations in K-ras with a particular gastric tumor histology implicates K-ras activation in the development of these tumors.