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

Biochem Biophys Res Commun. 2000 Nov 30;278(3):653-8. doi: 10.1006/bbrc.2000.3839.


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 substituting lysine (AAG) for normal glutamine (CAG) codon. Biological activity of this mutant K-ras gene was tested by expression of full-length cDNA clones in NIH3T3 cells. Most of the K-ras Lys22-transfected cells exhibited an increased saturation density, a lower serum requirement, and transformed morphology 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 number transformant produced tumors. Even though the activation is incomplete, the finding that the majority of tumor cells in the specimen carried the K-ras Lys22 mutation suggests that this mutation might be advantageous for growth of tumor cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adenine
  • Adenocarcinoma / genetics*
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic / genetics*
  • Colonic Neoplasms / genetics*
  • Cytosine
  • Genes, ras*
  • Humans
  • Lysine
  • Mice
  • Mice, Nude
  • Point Mutation*
  • Recombinant Proteins / biosynthesis
  • Transfection
  • Xenograft Model Antitumor Assays


  • Recombinant Proteins
  • Cytosine
  • Adenine
  • Lysine