AIM: This study quantified low-frequency KRAS mutations in normal lung and lung adenocarcinomas, to understand their potential significance in the development of acquired resistance to EGFR-targeted therapies. MATERIALS & METHODS: Allele-specific Competitive Blocker-PCR was used to quantify KRAS codon 12 GAT (G12D) and GTT (G12V) mutation in 19 normal lung and 21 lung adenocarcinoma samples. RESULTS: Lung adenocarcinomas had KRAS codon 12 GAT and GTT geometric mean mutant fractions of 1.94 × 10-4 and 1.16 × 10-3, respectively. For 76.2% of lung adenocarcinomas, the level of KRAS mutation was greater than the upper 95% confidence interval of that in normal lung. CONCLUSION: KRAS mutant tumor subpopulations, not detectable by DNA sequencing, may drive resistance to EGFR blockade in lung adenocarcinoma patients.
AIM: This study quantified low-frequency KRAS mutations in normal lung and lung adenocarcinomas, to understand their potential significance in the development of acquired resistance to EGFR-targeted therapies. MATERIALS & METHODS: Allele-specific Competitive Blocker-PCR was used to quantify KRAS codon 12 GAT (G12D) and GTT (G12V) mutation in 19 normal lung and 21 lung adenocarcinoma samples. RESULTS:Lung adenocarcinomas had KRAS codon 12 GAT and GTT geometric mean mutant fractions of 1.94 × 10-4 and 1.16 × 10-3, respectively. For 76.2% of lung adenocarcinomas, the level of KRAS mutation was greater than the upper 95% confidence interval of that in normal lung. CONCLUSION:KRAS mutant tumor subpopulations, not detectable by DNA sequencing, may drive resistance to EGFR blockade in lung adenocarcinomapatients.
Authors: Hiroko Sudo; Xiao-Cheng Li-Sucholeiki; Luisa A Marcelino; Amanda N Gruhl; Pablo Herrero-Jimenez; Helmut Zarbl; James C Willey; Emma E Furth; Stephan Morgenthaler; Hilary A Coller; Per O Ekstrom; Ray Kurzweil; Elena V Gostjeva; William G Thilly Journal: Mutat Res Date: 2008-09-09 Impact factor: 2.433
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