title: Low-frequencyKRASmutations are prevalent in lung adenocarcinomas.
abstract: OBJECTIVE
  This study quantified low-frequencyKRASmutations in normal lung and lung adenocarcinomas, to understand their potential significance in the development of acquired resistance to EGFR-targeted therapies.
  
  
  METHODS
  Allele-specific Competitive Blocker-PCR was used to quantifyKRAScodon 12 GAT (G12D) and GTT (G12V) mutation in 19 normal lung and 21 lung adenocarcinoma samples.
  
  
  RESULTS
  Lung adenocarcinomas hadKRAScodon 12 GAT and GTT geometric mean mutant fractions of 1.94 × 10-4and 1.16 × 10-3, respectively. For 76.2% of lung adenocarcinomas, the level ofKRASmutation was greater than the upper 95% confidence interval of that in normal lung.
  
  
  CONCLUSIONS
  KRASmutant tumor subpopulations, not detectable by DNA sequencing, may drive resistance to EGFR blockade in lung adenocarcinoma patients.
authors: Division of Genetic & Molecular Toxicology, US FDA, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors: Meagan B
authors: MB
authors: Myers
authors: Division of Genetic & Molecular Toxicology, US FDA, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors: Karen L
authors: KL
authors: McKim
authors: Division of Genetic & Molecular Toxicology, US FDA, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors: Fanxue
authors: F
authors: Meng
authors: Division of Genetic & Molecular Toxicology, US FDA, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors: Barbara L
authors: BL
authors: Parsons
keywords: carcinogenesis; epidermal growth factor receptor; mutation; mutation detection; non-small-cell lung cancer; oncogene; oncogene-induced senescence; personalized medicine; polyclonal tumor origin; targeted molecular therapy