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Clin Cancer Res. 2014 Aug 1;20(15):4107-14. doi: 10.1158/1078-0432.CCR-14-0284. Epub 2014 May 21.

FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.

Author information

1
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University;
2
Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University;
3
Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
4
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.
5
Department of Thoracic Surgery and Department of Oncology, Shanghai Medical College, Fudan University; sun_yihua76@hotmail.com hqchen1@yahoo.com hbji@sibcb.ac.cn.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

PMID:
24850843
DOI:
10.1158/1078-0432.CCR-14-0284
[Indexed for MEDLINE]
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