Open AccessEchinoderm microtubule‐associated protein‐like 4‐anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation coexisting in C hinese patients with lung adenocarcinoma
Author(s) -
Zhu Jianfei,
Cai Ling,
Yang Haoxian,
Wen Yinsheng,
Wang Junye,
Rong Tiehua,
Shao Jianyong,
Zhang Lanjun
Publication year - 2014
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12111
Subject(s) - kras , anaplastic lymphoma kinase , epidermal growth factor receptor , cancer research , medicine , mutation , gene rearrangement , fluorescence in situ hybridization , gene duplication , lung cancer , microbiology and biotechnology , biology , cancer , gene , genetics , chromosome , malignant pleural effusion
Background The echinoderm microtubule‐associated protein‐like 4‐anaplastic lymphoma kinase ( EML 4‐ ALK) rearrangement is almost in mutual exclusion to epidermal growth factor receptor ( EGFR) and v‐ K i‐ras2 K irsten rat sarcoma viral oncogene homolog ( KRAS) mutations, with rare exceptions. This study aimed to search for the coexisting gene alterations in C hinese patients with lung adenocarcinoma (LAC) . Methods We detected mutations in the EGFR , KRAS , and ALK gene rearrangements in samples from 131 C hinese 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 EML 4‐ ALK rearrangement were detected in this study. Our data was apparently inconsistent with the traditional view that the EML 4‐ ALK fusion gene in patients is resistant to EGFR ‐ TKIs .