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Published on: May 20, 2020
Mutations of the epidermal growth factor receptor gene in NSCLC patients
Bing Han1, Xiang Zhou, Rong-Xin Zhang
1Department of Respiration, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
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.
Insights
Epidermal growth factor receptor (EGFR) mutations are common in non-small cell lung cancer (NSCLC), particularly in non-smokers with adenocarcinoma. Some rare EGFR mutations, like P848L, do not respond to gefitinib treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) mutations are key drivers in non-small cell lung cancer (NSCLC).
- Identifying novel or rare EGFR mutations is crucial for understanding treatment resistance.
- EGFR mutations are frequently observed in lung adenocarcinoma, especially in non-smokers.
Purpose of the Study:
- To identify and characterize mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) patients.
- To evaluate the frequency of EGFR mutations and discover rare or novel variants.
- To assess the in vitro response of specific EGFR mutants to gefitinib treatment.
Main Methods:
- Sequencing of all 28 exons of the EGFR gene in 55 NSCLC patient samples.
- Construction of cDNA with P848L and T790M double mutants using site-directed mutagenesis.
- In vitro assessment of mutant EGFR response to gefitinib.
Main Results:
- EGFR mutations were detected in 8 out of 55 NSCLC patients.
- Six mutation-harboring patients with adenocarcinoma were non-smokers.
- The P848L mutant showed a similar response to wild-type EGFR, while the P848L/T790M double mutant exhibited high resistance to gefitinib.
Conclusions:
- EGFR mutations, including rare ones like P848L, are prevalent in lung adenocarcinoma, particularly in non-smokers.
- The P848L mutation alone does not confer resistance to gefitinib.
- Combined EGFR mutations (P848L/T790M) lead to gefitinib resistance, highlighting the need for personalized treatment strategies.
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