Abstract 4326: Co-amplification of FGF receptors and ligands in FGFR inhibitor-sensitive cell lines

The fibroblast growth factor receptors (FGFR) play a key role during development and in adult function. FGFRs belong to a family of receptor tyrosine kinases which are single-pass transmembrane receptors with extracellular ligand binding domains and an intracellular tyrosine kinase domain. Upon binding of the ligand the kinase domain activates intracellular signaling networks that coordinate cellular processes such as proliferation, growth, differentiation, migration and survival. Fibroblast growth factors (FGFs) are a family of 18 ligands which are able to bind and activate distinct FGFRs. Deregulated FGFR activity, through mutations or translocations, is often associated with oncogenic events. Overexpression of FGFR or FGF may lead to increased cell proliferation, growth, differentiation, migration or survival, thus making it an interesting target. In this study we optimized a TaqMan qRT-PCR-based approach to evaluate the copy number variation for several FGFRs (FGFR1, FGFR2, FGFR3 and FGFR4) and several FGF ligands (FGF1, FGF2, FGF3, FGF4, FGF10, FGF12, and FGF19) on a panel of 23 cell lines. The cell types covered a variety of diseases including bladder, breast, endometrial, gastric, kidney, liver, lymphoma, melanoma, sarcoma, small cell lung carcinoma and squamous cell carcinoma. These cell lines had been tested for sensitivity to the JNJ FGFR small molecule inhibitor JNJ42541707 which is a pan-FGFR inhibitor. We observed in the sensitive (IC50