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Updated: Mar 12, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Low-frequency KRAS mutations are prevalent in lung adenocarcinomas
Meagan B Myers1, Karen L McKim1, Fanxue Meng1
1Division of Genetic & Molecular Toxicology, US FDA, National Center for Toxicological Research, Jefferson, AR 72079, USA.
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.
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