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

It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations. This prospective study was a multicenter project conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including...

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Published inPloS one Vol. 10; no. 3; p. e0120852
Main Authors Hsu, Kuo-Hsuan, Ho, Chao-Chi, Hsia, Te-Chun, Tseng, Jeng-Sen, Su, Kang-Yi, Wu, Ming-Fang, Chiu, Kuo-Liang, Yang, Tsung-Ying, Chen, Kun-Chieh, Ooi, Hean, Wu, Tzu-Chin, Chen, Hung-Jen, Chen, Hsuan-Yu, Chang, Chi-Sheng, Hsu, Chung-Ping, Hsia, Jiun-Yi, Chuang, Cheng-Yen, Lin, Chin-Hung, Chen, Jeremy J. W., Chen, Kuan-Yu, Liao, Wei-Yu, Shih, Jin-Yuan, Yu, Sung-Liang, Yu, Chong-Jen, Yang, Pan-Chyr, Chang, Gee-Chen
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 19.03.2015
Public Library of Science (PLoS)
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Summary:It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations. This 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). From 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. 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.
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Conceived and designed the experiments: SLY CJY GCC. Performed the experiments: KHH CCH TCH KYS MFW KLC TYY KCC HO TCW HJC CPH JYH CYC CHL KYC WYL JYS. Analyzed the data: JST KYS HYC CSC. Contributed reagents/materials/analysis tools: JJC SLY CJY PCY GCC. Wrote the paper: KHH CCH TCH JST.
Competing Interests: The authors have declared that no competing interests exist.
These authors contributed equally to this work as co-corresponding authors.
These authors are co-first authors on this work.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0120852