Mutations Of The Epidermal Growth Factor Receptor Tyrosine Kinase Domain In Chinese Patients With Non-Small-Cell Lung Cancer

Objective: Therapy targeted EGFR has become another important modality for treatment NSCLC following surgery, radiotherapy and chemotherapy. But rate of tumor response to gefitinib, a specific EGFR tyrosine kinase inhibitor, was much lower than that of NSCLC with EGFR over-expression, and it has been demonstrated that the level of EGFR expression was not associated with tumor response. The discovery of mutations in EGFR tyrosine kinase domain revealed the mechanism mediating tumor response to gefitinib, and provided a powerful predictor for gefitinib therapy. In phase II clinical trial, tumor response to gefitinib was found more frequently in Japanese NSCLCs. Correspondingly, higher incidence of EGFR mutation was observed in NSCLC patients of Japanese origin compared with those of American origin, indicating different frequency of such mutation between different ethnics. Higher rate of tumor response to gefitinib was also found in Chinese NSCLCs, however, no data about such mutations in Chinese patients with NSCLC could be obtained. In the study we aimed to screen such mutations in Chinese NSCLCs and confirm the correlation between EGFR mutation and tumor response to gefitinib.Methods: Primary NSCLC tissues were obtained for analysis of mutations in exons 18-21 of EGFR from a total of 76 Chinese patients, of whom 54 did not receive gefitinib therapy and 22 did. All tumor tissues were obtained during diagnosis or surgical procedure before any treatment of lung cancer. PCR products were sequenced directly and mutations were confirmed by an independent PCR and sequence. All types of mutation were cloned and sequenced.Results: 29 mutations were found in 28 tumor tissues not including 2 types of silent mutation, in which included 15 deletion mutations and 14 missense mutations. All mutations can be divided into 8 types, in which 6 types of mutation were occurred in exon 19, 2 types of mutation (L858R and L861Q)were observed in exon 21. Among 6 types of deletion, 3 were simple deletions (delE746-A750; delL747-P753insS; del E746-T751insA), other 3 were deletions coupled with point mutations (delL747-E749, A750P, T751I; delL747-A750, T751P; delL747-S752, P753Q). 2 types of silent mutation (2361G>A, Q787Q; 2316C>T, P772P) were detected in exon 20.