Study On Mutation Profile And Frequency Of EGFR Exon 19 In Chinese Patients With Non-Small Cell Lung Cancer

Lung cancer is the serious health concern and leading cause of cancer deaths around the world.Non-small cell lung cancer?NSCLC?contributes 70-80% of lung cancer.Adenocarcinoma accounts for 50% and squamous cell carcinoma?SCC?22-30% of all NSCLC.Tyrosine Kinase Inhibitors?TKIs?are recommended as first line treatment for advanced NSCLC recently and significantly improves the treatment outcomes of lung adenocarcinoma patients with EGFR mutation.However,the application of TKI for lung squamous cell carcinoma?SCC?,second largest pathological subtype of NSCLC,remains controversial because available data of EGFR mutation profile and frequency in SCC patients is limited.In this study,first 89 bronchoscopies-biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation by improved PCR-DGGE.EGFR exon 19 mutations were detected in 77 of the 89?86.5%?patients,including six kinds of point mutations?11.6%?and two deletions Del₇47-751?64.9 %?and Del₇46-751?23.3%?.The proportion of mutated EGFR,varied from 0.98% to 100% in positive specimens,increased with the development of the disease.And the difference of proportion between stage IV patients and stage II patients or stage III patients was significant?P<0.001?.These results provided valuable clue to explain the reason why patients harboring same mutation responded distinctly to TKI treatment.Del₇47-751 and Del₇46-751 were dominant mutation in SCC patients and Del₇47-751 in?55.5%?EGFR positive patients was found less sensitive to TKI.However,assay of 45 adenocarcinoma patients revealed that the EGFR exon 19 mutation rate was 66.6%.And 55% EGFR positive adenocarcinoma patients harbored E746 deletion,TKI sensitive deletion.Meanwhile,four novel mutations,three-point mutation?c.2271 G>A?,?c.2237 A>G,c.2274 A>G?,?c.2199A>G c.2218 A>G?and one deletion combining point mutation?c.2235 G>A,c.2236 G>A,2237-2251_del?were identified in patients studied.Our study reveal the unique feature of EGFR mutation profile in Chinese NSCLC patients,which provide useful information for further probe the special molecular mechanism and treatment target of lung squamous cell carcinoma and adenocarcinoma.