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

<div><p>Background</p><p>It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations.</p><p>Methods</p><p>This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including <i>EGFR</i>, <i>KRAS</i>, <i>BRAF</i>, <i>HER2</i> and <i>EML4-ALK</i> fusion mutations, were tested. <i>EGFR</i>, <i>KRAS</i>, <i>BRAF</i> and <i>HER2</i> mutations were assessed by MALDI-TOF MS (Cohort 1). <i>EML4-ALK</i> translocation was tested by Ventana method in <i>EGFR</i>-wild type patients (Cohort 2).</p><p>Results</p><p>From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, <i>EGFR</i>, <i>KRAS</i>, <i>HER2</i> and <i>BRAF</i> 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 <i>EGFR</i> + <i>KRAS</i>, 3 with <i>EGFR</i> + <i>HER2</i> and 1 with <i>KRAS</i> + <i>BRAF</i>). In Cohort 2 analysis, 29 of 295 <i>EGFR</i>-wild type patients (9.8%) were positive for <i>EML4-ALK</i> translocation. <i>EGFR</i> mutations were more common in female patients and non-smokers and <i>KRAS</i> mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with <i>HER2</i>, <i>BRAF</i> and <i>EML4-ALK</i> mutations. <i>EML4-ALK</i> translocation was more common in patients with younger age.</p><p>Conclusion</p><p>This 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.</p>