Data from FGFR1/3 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Non–Small Cell Lung Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> 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 <i>FGFR</i> fusions.</p><p><b>Experimental Design:</b> Fourteen known <i>FGFR</i> fusion variants, including <i>FGFR1</i>, <i>FGFR2</i>, and <i>FGFR3</i>, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in <i>EGFR</i>, <i>KRAS</i>, <i>HER2</i>, <i>BRAF</i>, <i>ALK</i>, <i>RET</i>, and <i>ROS1</i>. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected.</p><p><b>Results:</b> Of 1,328 tumors screened, two (0.2%) were <i>BAG4-FGFR1</i> fusion and 15 (1.1%) were <i>FGFR3-TACC3</i> fusion. Six of 1,016 patients with lung adenocarcinoma were <i>FGFR3-TACC3</i> fusions and 11 of 312 lung squamous cell carcinoma harbored <i>BAG4-FGFR1</i> or <i>FGFR3-TACC3</i> fusions. Compared with the <i>FGFR</i> fusion-negative group, patients with <i>FGFR</i> fusions were more likely to be smokers (94.1%, 16 of 17 patients, <i>P</i> < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, <i>P</i> < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, <i>P</i> = 0.095).</p><p><b>Conclusions:</b><i>FGFR</i> fusions define a molecular subset of NSCLC with distinct clinical characteristics. <i>FGFR</i> is a druggable target and patients with <i>FGFR</i> fusions may benefit from <i>FGFR</i>-targeted therapy, which needs further clinical investigation. <i>Clin Cancer Res; 20(15); 4107–14. ©2014 AACR</i>.</p></div>