title: Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status.
abstract: BACKGROUND
  Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer.
  
  
  METHODS
  Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods.
  
  
  RESULTS
  524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant.
  
  
  CONCLUSIONS
  The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies.
authors: Guangdong Lung Cancer Institute, Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: She-Juan
authors: SJ
authors: An
authors: Zhi-Hong
authors: ZH
authors: Chen
authors: Jian
authors: J
authors: Su
authors: Xu-Chao
authors: XC
authors: Zhang
authors: Wen-Zhao
authors: WZ
authors: Zhong
authors: Jin-Ji
authors: JJ
authors: Yang
authors: Qing
authors: Q
authors: Zhou
authors: Xue-Ning
authors: XN
authors: Yang
authors: Ling
authors: L
authors: Huang
authors: Ji-Lin
authors: JL
authors: Guan
authors: Qiang
authors: Q
authors: Nie
authors: Hong-Hong
authors: HH
authors: Yan
authors: Tony S
authors: TS
authors: Mok
authors: Yi-Long
authors: YL
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate; D012907:Smoking / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors