Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients

Oncogene. 1993 Sep;8(9):2407-12.


Mutated K-ras oncogenes have been detected in a third of lung adenocarcinomas, located usually in codon 12, its presence correlating negatively with survival. To further define the role of K-ras point mutations in non-small cell lung cancer, we studied the presence of mutated K-ras genes in surgical specimens from 66 patients. Polymerase chain reaction was performed from sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13 and 61 of the K-ras gene by dot blot hybridization analysis with mutation-specific oligonucleotide probes. Ras gene mutations were present in 13 of 66 carcinomas (20%), nine in codon 12 and four in codon 61. Three squamous cell carcinomas harbored two different point mutations in K-ras codon 12. Mutated K-ras genes were found more frequently in squamous cell carcinomas (eight of 38) than in adenocarcinoma (three of 22). Analysis of nucleotide sequence disclosed a multifarious mutation pattern of K-ras codon 12, where the most common conversion was from glycine (GGT) to valine (GTT). K-ras point mutation positive subset had poorer survival, nine of the 13 patients died during the follow-up period as compared with 22 of 53 patients with no mutation in the K-ras gene (P = 0.01). The difference was also strikingly significant when stratified according to node status.

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Codon
  • Genes, ras*
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Point Mutation
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Survival Analysis


  • Codon
  • Oligodeoxyribonucleotides
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)