A novel activating mutation of the K-ras gene in human primary colon adenocarcinoma

We identified a novel type of point mutation at the 22nd codon of the K-ras gene in a primary colon cancer. The mutation was C to A transversion subst ituting lysine (AAG) for normal glutamine (CAG) codon. Biological activity of this mutant K-ras gene was tested by expression of full-length cDNA clon es in NIH3T3 cells. Most of the K-ras Lys22-transfected cells exhibited an increased saturation density, a lower serum requirement, and transformed mo rphology reminiscent to the typical K-ras Val12 transformants. However, the tumorigenicity of K-ras Lys22 transformants in nude mice was significantly less potent than that of K-ras Val12 transformants; only a high copy numbe r transformant produced tumors. Even though the activation is incomplete, t he finding that the majority of tumor cells in the specimen carried the K-r as Lys22 mutation suggests that this mutation might be advantageous for gro wth of tumor cells in vivo. (C) 2000 Academic Press.