Identification of Five Driver Gene Mutations in Patients with Treatment-Naïve Lung Adenocarcinoma in Taiwan

Abstract

BackgroundIt is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations.MethodsThis prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2).ResultsFrom August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age.ConclusionThis was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials.

Factors associated with the prognosis and long-term survival of patients with metastatic lung adenocarcinoma: a retrospective analysis

“…Such distinct response to gefitinib suggested that LTS group in our study is very likely a group of EGFR-mutant lung adenocarcinoma. Anaplastic lymphoma kinase (ALK) fusion oncogene is an emerging molecular target in lung adenocarcinoma (30), which accounts for 3-5% of genetic alteration (12,31,32). Patients with ALK fusion oncogene were characterized by younger age, non-smoking status and good response to several TKIs (33).…”

“…Furthermore, patients with advanced NSCLC harboring oncogenic driver mutation had better survival outcome as comparing to patients without driver mutation (10,11). In Asia-Pacific region, EGFR exon 18-21 mutation is the most common type of oncogenic mutation in lung adenocarcinoma, with incidence rate of 55% (12). Tyrosine kinase inhibitors (TKIs) targeting EGFR had been shown to improve progression-free survival in patients with advanced NSCLC harboring sensitive EGFR mutation status in first line setting (13)(14)(15)(16)(17)(18)(19)(20).…”

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…BRAF p.V600E mutation is more frequent in females 52,54 and never smokers 54 in some studies, but several studies failed to show these associations. 49,50,53,58 One distinction between BRAF mutations and other Figure 1 Forest plot of sensitivity and specificity for immunohistochemistry (IHC)-based determination of ROS1 rearrangement positivity compared with fluorescence in situ hybridization. Pooled estimate of sensitivity and specificity based on bivariate analysis of included studies.…”

“…FN, false-negative; FP, false-positive; TN, true-negative; TP, true-positive. jmd.amjpathol.org -The Journal of Molecular Diagnostics targetable oncogenes is that non-p.V600E BRAF mutations (particularly the exon 11 mutations) may coexist with mutations in KRAS, 49,52,53,59 whereas the p.V600E mutations are mutually exclusive of KRAS, EGFR, or ALK alterations.…”

“…95 Five studies attempted to identify associations between patient or tumor characteristics and KRAS mutational status. 49,52,92,93,95 Two MAs 93,94 reported on overall survival and EGFR-TKI response rates when KRAS mutationepositive patients were treated with standard care. All included studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' findings (SDC Table 16).…”