Authors

Chenglin Li*, Fengfeng Zhou**, #

Departments

*Department of Oncology, Linyi People’s Hospital, Linyi, PR China - **Department of Infectious Disease, Linyi People’s Hospital, Linyi, PR China

Abstract

Objective: Non-small cell lung cancer (NSCLC) carrying EGFR gene-activated mutations is highly sensitive to EGFR-specific tyrosine kinase inhibitors. However, most patients who initially responded were still progressing during subsequent treatment. This ‘acquired resistance’ can be attributed, in part, to the secondary mutation that produced threonine at codon 790 (T790M) of the EGFR gene and subsequently changed to methionine.

Methods: Exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene were sequenced to identify secondary mutant tumours with acquired resistance to gefitinib in 14 patients with non-small cell lung adenocarcinoma. Besides normal sequencing, subcloning or cyclic PCR is used to improve the sensitivity of detection. We also looked for T790M and secondary KRAS mutations in 52 pre-treated samples from patients treated with gefitinib, because tumours with KRAS mutations are usually resistant to tyrosine kinase inhibitors.

Results: Seven of the 14 tumours had a secondary T790M mutation. There were no other new secondary mutations. The T790M mutation was not detected in five pre-treated specimens of the seven tumours available. T790M patients are often women, non-smokers, and carriers of deletion mutations, but T790M is not related to the duration of gefitinib administration. None of the 14 tumours had acquired mutations in the KRAS gene.

Conclusion: Secondary T790M mutation of EGFR accounts for half of the gefitinib-resistant acquired tumours. Other secondary mutations of drug resistance are not common in the EGFR gene.

Keywords

Non-small cell lung cancer, epidermal growth factor receptor (EGFR), gefitinib, drug resistance.

DOI:

10.19193/0393-6384_2020_3_232