Oncotarget

Research Papers:

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

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Oncotarget. 2015; 6:34300-34308. https://doi.org/10.18632/oncotarget.5549

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Abstract

Rui Wang1,2,*, Yang Zhang1,2,*, Yunjian Pan1,2, Yuan Li2,3, Haichuan Hu1,2, Deng Cai1,2, Hang Li1,2, Ting Ye1,2, Xiaoyang Luo1,2, Yiliang Zhang1,2, Bin Li1,2, Lei Shen2,3, Yihua Sun1,2, Haiquan Chen1,2,4,5

1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

4Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

5Institutes of Biomedical Sciences, Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Haiquan Chen, e-mail: [email protected]

Yihua Sun, e-mail: [email protected]

Keywords: non-small cell lung cancer, driver mutations, ERBB, FGFR

Received: July 22, 2015     Accepted: September 10, 2015     Published: October 12, 2015

ABSTRACT

Purpose: To determine the frequency of driver mutations in Chinese non-small cell lung cancer (NSCLC) patients.

Methods: Comprehensive 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.

Results: Mutations 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).

Conclusion: We 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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