Mutations of the epidermal growth factor receptor gene in NSCLC patients

Han,Bing; Zhou,Xiang; Zhang,Rong-Xin; Zang,Wang-Fu; Chen,Zhong-Yuan; Song,Huai-Dong; Wan,Huan-Ying; Zheng,Cui-Xia

doi:10.3892/ol.2011.366

Mutations of the epidermal growth factor receptor gene in NSCLC patients

Authors:
- Bing Han
- Xiang Zhou
- Rong-Xin Zhang
- Wang-Fu Zang
- Zhong-Yuan Chen
- Huai-Dong Song
- Huan-Ying Wan
- Cui-Xia Zheng
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Affiliations: Department of Respiration, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China, Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China, Department of Oncosurgery, Bengbu Medical College, Bengbu, P.R. China, Center of Molecular Medicine, Shanghai Institute of Endocrinology, State Key Laboratory of Medical Genomics, Shanghai, P.R. China, Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
Published online on: July 25, 2011 https://doi.org/10.3892/ol.2011.366
Pages: 1233-1237

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Abstract

Mutations of the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) were identified by re-sequencing all exons of this gene to evaluate the frequencies of EGFR gene mutation and identify rare or novel EGFR mutations. A total of 55 NSCLC samples from 55 patients were included in the study. Genomic DNA was extracted and exons 1-28 of the EGFR gene were sequenced to identify mutations. The cDNA of the EGFR gene with P848L and T790M double mutants was constructed by introducing point mutations into the wild‑type EGFR vector using a site‑directed mutagenesis kit. Among the 55 patients with NSCLC, 8 patients carried mutations of the EGFR gene. Notably, of the mutation‑harboring patients with a pathological type of adenocarcinoma, 6 were non-smokers. The in vitro study demonstrated that the P848L mutant had a similar response to that of the wild‑type EGFR after gefitinib treatment, and the P848L and T790M double mutant exhibited high resistance to gefitinib. These EGFR mutations preferentially occurred in lung adenocarcinoma patients, most of whom were non‑smokers. In the in vitro study, P848L mutant EGFR had a similar response as the wild‑type EGFR to gefitinib treatment, suggesting that lung cancer patients with a rare mutation of EGFR, such as the P848L mutation, do not respond to gefitinib treatment.

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