title: Evaluation of Kras gene mutation and copy number gain in non-small cell lung cancer.
abstract: BACKGROUND
  Recent studies for the characterization of the lung cancer genome have suggested that Kras gene was frequently amplified and correlated with activating mutations of Kras, which occur in approximately 5 to 10% of Japanese lung cancers.
  
  
  METHODS
  We analyzed Kras mutation and Kras copy number in 172 Japanese non-small cell lung cancer (NSCLC) cases and their relation to the survival of patients. We also studied using fluorescence in situ hybridization to provide direct evidence of Kras amplification in 40 clinical specimens.
  
  
  RESULTS
  In 172 NSCLC cases, increased Kras copy number existed in 19 (11.0%) cases. Increased Kras gene copy number was correlated with Kras mutation. Nevertheless, Kras gene copy number gain was not correlated with gender, pathological subtypes, stages, and smoking status. Increased Kras copy number was not associated with overall survival in these 172 cases; however, patients with increased Kras copy number and Kras mutant had significantly worse prognosis, when compared with patients with Kras wild type and Kras not increased. From the fluorescence in situ hybridization analysis, Kras polysomy or amplified patients showed significantly worse prognosis, when compared with Kras disomy patients.
  
  
  CONCLUSIONS
  Kras mutation plus increased copy number was a predictor of poor clinical outcome in patients with NSCLC.
authors.affiliation: Department of Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Hikosaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawano
authors.forename: Satoru
authors.initials: S
authors.lastname: Moriyama
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins