EGFR mutations in patients with lung adenocarcinoma in southwest China: are G719S/A and L861Q more likely detected in tumors derived from smokers?

Abstract

Background:The clinical characteristics of epidermal growth factor receptor (EGFR) hotspot mutations, such as deletions in exon 19, substitution of L858R in exon 21, and mutations in exon 20, have been widely reported in nonsmall cell lung cancer. However, the clinical features of other low frequency EGFR mutations in these four exons (especially the relationship with smoking history), eg, substitutions of G719S/A/C in exon 18 and L861Q in exon 21, remain unclear. This study investigated the relationship between G719S/A/C and L861Q mutations (in exon 18 and 21) and smoking history. Methods: Specimens from 194 patients with lung adenocarcinoma were analyzed for EGFR mutations in exons 18-21 by high-resolution melting curve analysis and amplification refractory mutation technology to establish the relationship between G719S/A/C and L861Q mutations and smoking history. Results: Ninety-six of 194 tumors (49.5%) were confirmed to be EGFR mutation-positive. Among these mutations, 71 of 104 (68.3%) were from never smokers, six of 17 (35.3%) were from former smokers, and 19 of 73 (26.0%) were from current smokers (P , 0.001). The mutation rate in heavy smokers (5/23, 21.7%) was significantly lower than in light smokers (20/67, 29.9%) and never smokers (71/104, 68.3%, P , 0.001). Seven low frequency EGFR mutations (four substitutions of G719S, and G719 A, respectively, and three of L861Q in exon 21) were identified. Five of these mutations were derived from smokers (one former light smoker, one current heavy smoker, and three current light smokers). Four of these patients had been treated with tyrosine kinase inhibitors and all had a partial response, with median overall survival (14.5 months) and median progression-free survival (6.8 months), being longer than in patients with similarly staged lung adenocarcinoma without EGFR mutation or treatment with tyrosine kinase inhibitors (6.8 and 3.1 months, respectively, according to data from an as yet unpublished study at our institution). Conclusion:This study provides further evidence that smoking status, include years of smoking and number of cigarettes smoked per day, plays an important role in EGFR mutation in patients with lung adenocarcinoma. Five of seven specimens with G719S/A or L861Q mutations coming from smokers indicates that there may be a relationship between G719S/A or L861Q mutation and smoking history. However, regardless of the influence of smoking, the effectiveness of tyrosine kinase inhibitors was satisfactory in four patients harboring G719S/A and L861Q EGFR mutation.

Uncommon <em>EGFR</em> mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

“…33 Our data showed that male patients (65%; p <0.05) had higher rate of EGFR uncommon mutations than female patients (35%), which may be partly explained by recent descriptive studies suggesting putative association between uncommon mutations (G719X and L861Q) and smoking history. 34 , 35 Therefore, future studies are needed to clarify definite association between EGFR uncommon mutations and smoking history in Indonesian lung cancer patients.…”

Biological Significance of 18F-FDG PET/CT Maximum Standard Uptake Value for Predicting EGFR Mutation Status in Non-Small Cell Lung Cancer Patients

“…EGFR mutation test was performed on tissue biopsies of all patients using an amplification refractory mutation system (ARMS) with the ADx-ARMS EGFR Mutation Test Kit (Amoy Diagnostics Co., Ltd., Xiamen, China) as previously described. 23 …”