Analysis of Epidermal Growth Factor Receptor Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib

摘要: Purpose: Non–small cell lung cancers carrying activating mutations in the gene for epidermal growth factor receptor (EGFR) are highly sensitive to EGFR-specific tyrosine kinase inhibitors. However, most patients who initially respond subsequently experience disease progression while still on treatment. Part of this “acquired resistance” is attributable a secondary mutation resulting threonine methionine at codon 790 (T790M) EGFR. Experimental Design: We sequenced exons 18 21 EGFR look tumors with acquired resistance gefitinib 14 adenocarcinomas. Subcloning or cycleave PCR was used addition normal sequencing increase sensitivity assay. also looked T790M pretreatment samples from 52 were treated gefitinib. KRAS because generally resistant Results: Seven had mutation. There no other novel mutations. detected specimens available five among these seven tumors. Patients tended be women, never smokers, and deletion mutations, but not associated duration administration. None an gene. Conclusions: A accounted half Japanese patients. Other drug-resistant uncommon