Clinical significance of functional driver gene mutations in patients with non-small cell lung cancer

Abstract

Objective To investigate the mutational status of functional driver genes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase(ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf protooncogene serine /threonine protein kinase (BRAF) in non-small cell lung cancer (NSCLC) patients. Methods Specimens from surgery, lymph node biopsy, needle biopsy of lung, bronchoscopy biopsy and pleural effusion cells were collected in 203 (NSCLC) patients. EGFR, KRAS, and BRAF mutations were analyzed by amplification refractory mutation system(ARMS). ALK fused gene was detected by immunohistochemistry(IHC). The relationships between the mutations and the clinicopathologic features were further evaluated by Chi-squared test. Results The mutation rates of EGFR, ALK, KRAS and BRAF were 51.23%(104/203), 4.88%(8/164), 10.69%(17/159), 1.26%(2/159) respectively. The positive mutation rate of EGFR was 66.67% in females compared with 36.21% in males, 48.80% in adenocarcinoma compared with 33.33% in squamous carcinoma, and 63.38% in non-smokers compared with 16.39% in smokers. The mutation rates of EGFR were significantly different with gender, histological type, age and smoking history (χ2=18.45, 113.13, 37.69, all P 0.05). However, no evident associations were found between ALK, KRAS gene mutations and gender, as well as histological type, age and smoking history (χ2=0.00, 0.86, 0.55, all P>0.05) (χ2=3.63, 2.13, 2.36, all P>0.05). In addition, the mutation rate of BRAF was higher in male and smoker. The double mutation of EGFR in exons 19 and 21 was found in 3 cases, only 1 case with double mutation of EGFR and ALK was found. Conclusion The mutation rate of EGFR, associated with gender, pathohistology and smoking habits, was higher than KARS, ALK and BRAF in patients with NSCLC. Key words: Carcinoma, non-small cell lung; Genes, erbB-1; Genes, ras; Proto-oncogene proteins B-raf; DNA mutational analysis