Data from The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing

<div>Abstract<p><b>Purpose:</b> Molecular profiling may have prognostic and predictive value, and is increasingly used in the clinical setting. There are more than a dozen fibroblast growth factor receptor (FGFR) inhibitors in development. Optimal therapeutic application of FGFR inhibitors requires knowledge of the rates and types of FGFR aberrations in a variety of cancer types.</p><p><b>Experimental Design:</b> We analyzed frequencies of FGFR aberrations in 4,853 solid tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One.</p><p><b>Results:</b> FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplification (66% of the aberrations), followed by mutations (26%) and rearrangements (8%). <i>FGFR1</i> (mostly amplification) was affected in 3.5% of 4,853 patients; <i>FGFR2</i> in 1.5%; <i>FGFR3</i> in 2.0%; and <i>FGFR4</i> in 0.5%. Almost every type of malignancy examined showed some patients with FGFR aberrations, but the cancers most commonly affected were urothelial (32% FGFR-aberrant); breast (18%); endometrial (∼13%), squamous lung cancers (∼13%), and ovarian cancer (∼9%). Among 35 unique FGFR mutations seen in this dataset, all but two are found in COSMIC. Seventeen of the 35 are known to be activating, and 11 are transforming.</p><p><b>Conclusions:</b> FGFR aberrations are common in a wide variety of cancers, with the majority being gene amplifications or activating mutations. These data suggest that FGFR inhibition could be an important therapeutic option across multiple tumor types. <i>Clin Cancer Res; 22(1); 259–67. ©2015 AACR</i>.</p></div>