Epidermal growth factor receptor mutation in serum circulating DNA and selective targeting therapy against lung cancer

Objective:To detect somatic mutations in epidermal growth factor receptor(EGFR) in the serum circulating DNA,screen the EGFR-mutated lung cancer patients,and evaluate the clinical effects of the genetically targeted drug gefitinib.Methods:DNA was extracted from the serum specimens of patients and amplified by PCR.The EGFR mutations in PCR product were detected by direct sequence analysis.Results:Somatic mutations of EGFR were identified in serum from 46 of the 116 cases(39.7%),including 30 cases(65.2%) in exon 19 and 16 cases(34.8%) in exon 21.Female patients and those patients with adenocarcinoma(including adenosquamous carcinoma) had an increased frequency of mutations.Further analysis on 20 lung cancer patients demonstrated that the EGFR mutation in serum was consistant with that detected in tumor tissues,suggesting that the EGFR mutations in serum originated from the primary tumor.Based on the screening assay,19 patients with EGFR mutations who failed prior chemotherapy were treated with gefitinib.The response rate was 52.6% and the disease-controlling rate was 89.5%.The median progression-free survival time was 8 months,the median overall survival time was 12 months,and 2-year survival rate was 33.3%.Conclusions:The EGFR mutations in serum circulating DNA are consistant with the mutation in lung cancer tissue.Gefitinib treatment has significant effects on the advanced lung cancer based on the screening results of EGFR mutation.