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


CONCLUSIONS
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.
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Rui
R
Wang
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Yang
Y
Zhang
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Yunjian
Y
Pan
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Yuan
Y
Li
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Haichuan
H
Hu
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Deng
D
Cai
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Hang
H
Li
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Ting
T
Ye
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Xiaoyang
X
Luo
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Yiliang
Y
Zhang
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Bin
B
Li
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Lei
L
Shen
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Yihua
Y
Sun
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Haiquan
H
Chen
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
ERBB; FGFR; driver mutations; non-small cell lung cancer