• Oncotarget · Oct 2015

    Comprehensive investigation of oncogenic driver mutations in Chinese non-small cell lung cancer patients.

    • Rui Wang, Yang Zhang, Yunjian Pan, Yuan Li, Haichuan Hu, Deng Cai, Hang Li, Ting Ye, Xiaoyang Luo, Yiliang Zhang, Bin Li, Lei Shen, Yihua Sun, and Haiquan Chen.
    • Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
    • Oncotarget. 2015 Oct 27; 6 (33): 34300-8.

    PurposeTo determine the frequency of driver mutations in Chinese non-small cell lung cancer (NSCLC) patients.MethodsComprehensive mutational analysis was performed in 1356 lung adenocarcinoma, 503 squamous cell carcinoma, 57 adenosquamous lung carcinoma, 19 large cell carcinoma and 8 sarcomatoid carcinoma. The effect of EGFR tyrosine kinase inhibitors (TKIs) on EGFR-mutated lung adenocarcinoma patients after disease recurrence was investigated.ResultsMutations in EGFR kinase domain, HER2 kinase domain, KRAS, BRAF, ALK, ROS1 and RET were mutually exclusive. In lung adenocarcinoma cases "pan-negative" for the seven above-mentioned driver mutations, we also detected two oncogenic EGFR extracellular domain mutations (A289D and R324L), two HER2 extracellular and transmembrane domain mutations (S310Y and V659E), one ARAF S214C mutation and two CD74-NRG1 fusions. Six (1.2%) FGFR3 activating mutations were identified in lung squamous cell carcinoma (five S249C and one R248C). There were three (15.8%) EGFR mutations and four (21.1%) KRAS mutations in large cell carcinoma. Three (37.5%) KRAS mutations were detected in sarcomatoid carcinoma. In EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence, treatment with EGFR TKIs was an independent predictor of better overall survival (HR = 0.299, 95% CI: 0.172-0.519, P < 0.001).ConclusionWe determined the frequency of driver mutations in a large series of Chinese NSCLC patients. EGFR TKIs might improve the survival outcomes of EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence.

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