Low-frequency KRAS mutations are prevalent in lung adenocarcinomas

被引：17

作者：

Myers, Meagan B. ^{[1
]}

McKim, Karen L. ^{[1
]}

Meng, Fanxue ^{[1
]}

Parsons, Barbara L. ^{[1
]}

机构：

[1] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA

来源：

PERSONALIZED MEDICINE | 2015年 / 12卷 / 02期

关键词：

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; TYROSINE KINASE INHIBITORS; GROWTH-FACTOR RECEPTOR; K-RAS MUTATIONS; ACB-PCR QUANTIFICATION; ACQUIRED-RESISTANCE; MUTANT FRACTION; PERSONALIZED THERAPY; CANCER CELLS; PHASE-III; EGFR;

D O I：

10.2217/PME.14.69

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 x 10(-4) and 1.16 x 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.

引用

页码：83 / 98

页数：16

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