Clinicopathologic Significance of the K-ras Gene Codon 12 Point Mutation in Stomach Cancer. An Analysis of 140 Cases

Cancer. 1995 Jun 15;75(12):2794-801. doi: 10.1002/1097-0142(19950615)75:12<2794::aid-cncr2820751203>;2-f.


Background: The frequency and clinicopathologic significance of the K-ras gene point mutation in stomach cancer remain to be defined.

Methods: The authors investigated the frequency of K-ras codon 12 point mutations in stomach cancer using a sensitive polymerase chain reaction (PCR)-based method in 140 samples and correlated the findings with various clinicopathologic characteristics of the patients.

Results: The overall frequency of K-ras codon 12 point mutations in stomach cancer was 7.9% (11/140). DNA sequencing of nine cases with K-ras codon 12 point mutations identified seven cases with a single-base substitution of GGT to AGT (glycine to serine) and two with single-base substitution of GGT to AGT (aspartic acid). Tumors located in the upper third of the stomach had a significantly higher frequency of K-ras codon 12 mutations (3/8, 37.5%) compared with tumors located in the middle (4/29, 13.8%) or lower (3/99, 3.0%) thirds of the stomach (P = 0.001). No significant difference was observed in the frequency of K-ras codon 12 mutations in terms of other various clinicopathologic characteristics including tumor DNA ploidy and S-phase fraction. After a median follow-up of 26 months, disease free and overall survival were not significantly different between patients with stomach cancer with or without K-ras codon 12 mutation. Among eight patients with stomach cancer located in the upper part of the stomach, none of the three patients with K-ras gene-mutated tumors died versus four of five with tumors without K-ras gene mutations (P = 0.064).

Conclusions: K-ras codon 12 point mutations are uncommon in stomach cancer (7.9%). There was significant correlation between K-ras mutations and vertical tumor location in the stomach, suggesting that different mechanisms may play a role in the pathogenesis of stomach cancer according to the location of tumors in the stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Codon*
  • DNA, Neoplasm / analysis
  • Female
  • Flow Cytometry
  • Genes, ras*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Point Mutation*
  • Polymorphism, Restriction Fragment Length
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology


  • Codon
  • DNA, Neoplasm