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Lung cancer,predominantly the non-small cell lung cancer(NSCLC) is the leading cause of cancer mortality worldwide.Although smoking is the major risk factor for lung cancer,there are at least more than 25% of lung cancer cannot be attributable to smoking.Cumulated evidence has shown that lung cancer in non-smokers is a distinct disease with high prevalence in female gender,high adenocarcinoma cell type,and high EGFR mutations.The global increase of lung cancer in non-smoker,particularly in lung adenocarcinoma,is an emerging health threatening especially in East Asia.The major driver genes of non-smoker adenocarcinoma may be identified.The identification of EGFR activating mutations(>50%)and EML4-ALK(5-10%) rearrangement as the major driver genetic changes in lung adenocarcinoma and the development of effective targeted therapy with specific kinase inhibitors are the major breakthroughs and have shed light for the possibility of personalized therapy based on the genotyping.However,there are some unsolved issues in implementing the gene testing for personalized lung cancer therapy.Given the well-recognized EGFR gene testing for example,the standardization and accreditation of gene testing methodology may be crucial for quality assurance.Not all EGFR mutations are the same.The Del 19 and exon 21(L858R) are the most sensitive mutations and exon 20 mutations are the resistant mutations.