title: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation coexisting in Chinese patients with lung adenocarcinoma.
abstract: BACKGROUND
  The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement is almost in mutual exclusion to epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, with rare exceptions. This study aimed to search for the coexisting gene alterations in Chinese patients with lung adenocarcinoma (LAC).
  
  
  METHODS
  We detected mutations in the EGFR, KRAS, and ALK gene rearrangements in samples from 131 Chinese patients with LAC. ALK rearrangements were identified by fluorescent in situ hybridization. Mutations in EGFR (exons 19 to 21) and KRAS (codons 12 and 13) were determined by real time polymerase chain reaction.
  
  
  RESULTS
  All patients were classified into four distinct genotype groups: EGFR mutations (n = 63; 48.1%), ALK rearrangements (n = 9; 6.9%), KRAS mutations (n = 8; 6.1%), and the wild-type (unmutated) genotype of all three genes (WT/WT/WT) (n = 53; 40.5%). Interestingly, two never-smoking women (2/131, 1.5%) harbored coexisting ALK rearrangement and EGFR mutation. ALK rearrangement occurred more frequently in young patients (8/9) (P = 0.687), non-smokers (8/9) (P = 0.077), and those who had no family history of LAC (8/9) (P = 1.000); all KRAS mutations occurred in the EGFR wild type (P = 0.007). KRAS mutations were generally detected in young patients (6/8) (P = 0.658) and in those who had no family history (7/8) (P = 1.000); EGFR mutations correlated with gender (P = 0.001), and smoking status (P < 0.001).
  
  
  CONCLUSIONS
  Two patients harboring both EGFR mutation and EML4-ALK rearrangement were detected in this study. Our data was apparently inconsistent with the traditional view that the EML4-ALK fusion gene in patients is resistant to EGFR-TKIs.
authors.affiliation: Sun Yat-sen University Cancer CenterGuangzhou, Guangdong, China; Shaanxi Provincial People's HospitalXi'an, Shaanxi, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cai
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Haoxian
authors.initials: H
authors.lastname: Yang
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Junye
authors.initials: J
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Tiehua
authors.initials: T
authors.lastname: Rong
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Shao
authors.affiliation: Sun Yat-sen University Cancer Center Guangzhou, Guangdong, China.
authors.forename: Lanjun
authors.initials: L
authors.lastname: Zhang
keywords: Coexisting; EGFR; EML4-ALK; K-RAS; lung cancer