title: Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases.
abstract: 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.
authors.affiliation: Department of Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Suh
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.forename: S B
authors.initials: SB
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: M Y
authors.initials: MY
authors.lastname: Park
authors.forename: H S
authors.initials: HS
authors.lastname: Sun
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D003062:Codon; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D003062:Codon; D004273:DNA, Neoplasm