FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.
OBJECTIVE
The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions.


METHODS
Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected.


RESULTS
Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095).


CONCLUSIONS
FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation.
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Rui
R
Wang
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Lei
L
Wang
Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University;
Yuan
Y
Li
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Haichuan
H
Hu
Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University;
Lei
L
Shen
Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University;
Xuxia
X
Shen
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Yunjian
Y
Pan
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Ting
T
Ye
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Yang
Y
Zhang
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Xiaoyang
X
Luo
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Yiliang
Y
Zhang
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Bin
B
Pan
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Bin
B
Li
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Hang
H
Li
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
Jie
J
Zhang
Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
William
W
Pao
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science, Shanghai, China; and sun_yihua76@hotmail.com hqchen1@yahoo.com hbji@sibcb.ac.cn.
Hongbin
H
Ji
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University; sun_yihua76@hotmail.com hqchen1@yahoo.com hbji@sibcb.ac.cn.
Yihua
Y
Sun
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University; sun_yihua76@hotmail.com hqchen1@yahoo.com hbji@sibcb.ac.cn.
Haiquan
H
Chen
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D048868:Adaptor Proteins, Signal Transducing; C116906:BAG4 protein, human; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C120551:TACC3 protein, human; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3