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Low-frequency KRAS mutations are prevalent in lung adenocarcinomas.

ABSTRACT:

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.

SUBMITTER: Myers MB

PROVIDER: S-EPMC5084916 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Low-frequency <i>KRAS</i> mutations are prevalent in lung adenocarcinomas.

Myers Meagan B MB McKim Karen L KL Meng Fanxue F Parsons Barbara L BL

Personalized medicine 20150301 2

<h4>Aim</h4>This study quantified low-frequency <i>KRAS</i> mutations in normal lung and lung adenocarcinomas, to understand their potential significance in the development of acquired resistance to EGFR-targeted therapies.<h4>Materials & methods</h4>Allele-specific Competitive Blocker-PCR was used to quantify <i>KRAS</i> codon 12 GAT (G12D) and GTT (G12V) mutation in 19 normal lung and 21 lung adenocarcinoma samples.<h4>Results</h4>Lung adenocarcinomas had <i>KRAS</i> codon 12 GAT and GTT geome ...[more]

PMID: 27795727

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