title: EGFR,ALK,RET,KRASandBRAFalterations in never-smokers with non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies for the treatment of NSCLC.
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Dong
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450000, P.R. China; Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Thoracic Surgery, Chongqing Cancer Institute, Chongqing 400040, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
authors.forename: B O
authors.initials: BO
authors.lastname: Jin
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Yuanqi Bio-Pharmaceutical Company Ltd., Shanghai 201403, P.R. China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Tao
authors.affiliation: Shanghai Yuanqi Bio-Pharmaceutical Company Ltd., Shanghai 201403, P.R. China.
authors.forename: Ren
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Qinxian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
keywords: ALK; BRAF; EGFR; KRAS; RET; lung cancer; never-smokers