Epidermal growth factor receptor P848L mutation and its function in non-small-cell lung cancer

Objective: To determine the mutation status of epidermal growth factor receptor (EGFR) in chinese non-small-cell lung cancer (NSCLC) patients,and after detected a rare mutant type of EGFR,P848L,to further study its functional feature.Methods: Fiftyfive NSCLC samples were enrolled in the study.The total DNA was extracted,then the 1-27 exons were sequenced for the detection of mutation.The P848L mutant EGFR construct and then the T790M mutation was generated by introducing a point mutation into the wildtype EGFR vector using a site-directed mutagenesis kit.Results: There were 8 cases of mutations being detected,all the mutationharboring patients were non-smoker with pathologic type of adenocarcinoma.In vitro study demonstrated that the P848L mutant had a similar response to gefitinib treatment,and P848L and T790M double mutant did respond to gefitinib.Conclusions: EGFR mutations occurred in only non-smoker patients with lung adenocarcinoma in this series.P848L mutant EGFR has a similar response as the widetype to gefitinib treatment,while double mutated with T790M diminished the response completely.