title: Detection of low-fraction K-ras mutations in primary lung tumors using a sensitive method.
abstract: Mutations in the K-ras gene are often identified in lung tumors and are implicated in the development of lung cancer. We used a sensitive method to analyze low-fraction mutations occurring in codon 12 of the K-ras gene in 114 primary lung tumors, including 77 adenocarcinomas, 31 squamous cell carcinomas and 6 adenosquamous carcinomas, which had previously been shown to be negative for codon 12 K-ras mutation in a first screening using less sensitive methods. Sixteen of these tumors were found to contain a low-fraction mutation, including 9 mutations among the adenocarcinomas, six mutations among the squamous cell carcinomas and one mutation among the adenosquamous carcinomas. Our study also showed that the occurrence of low-fraction mutation was associated with a positive smoking history, as was previously found for the occurrence of high-fraction mutation. Patients with low-fraction mutations were younger (mean age 58.8 years) than those with either high-fraction mutations (63.2 years) or no mutation (66 years). Patients with low-fraction mutations were more often stage 1 (8 of 10) than patients with either high fraction mutations (22 of 44) or no mutation (33 of 71). Moreover, the overall survival was better for the group with a low-fraction mutation than both the high-fraction mutation group and the group with no K-ras mutation, but due to small sample size, the difference was not statistically significant. Our results suggest that using highly sensitive methods of K-ras mutant detection in tumor DNA could obscure differences between patients in whom the mutation is found throughout the tumor, those in whom the mutation is only present in a small subpopulation and those who have no mutation.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA. pho1.vms.cis.pitt.edu.
authors.forename: P
authors.initials: P
authors.lastname: Keohavong
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.forename: A C
authors.initials: AC
authors.lastname: Melacrinos
authors.forename: M A
authors.initials: MA
authors.lastname: DeMichele
authors.forename: R J
authors.initials: RJ
authors.lastname: Weyant
authors.forename: J D
authors.initials: JD
authors.lastname: Luketich
authors.forename: J R
authors.initials: JR
authors.lastname: Testa
authors.forename: M
authors.initials: M
authors.lastname: Fedder
authors.forename: J M
authors.initials: JM
authors.lastname: Siegfried
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D004586:Electrophoresis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D003062:Codon