Glioblastoma multiforme is the most common of adult primary brain tumors. It is a highly aggressive form of diffuse gliomas and with current treatments median life expectancy of patients with glioblastoma is approximately 14 months. Resent research of genetic and molecular changes in glioblastoma has provided new insight on disease initiation and progression. Fibroblast growth factor receptor 3 gene fusion with transforming acidic coiled coil 3 (FGFR3:TACC3) was found in subset of glioblastomas and has been shown to increase proliferation and anchorage independent growth of tumor cells. It is known to be mutually exclusive with other growth factor receptor alterations so it seems to be providing alternative pathway for tumor formation. However, FGFR3:TACC3 is usually not one of the initiating alterations in glioblastoma. Inhibition of FGFR in fusion positive tumors has shown promising results in vitro and in preclinical studies.

The aim of this study was compare cellular mechanisms between SNB19 glioblastoma cells that had been stably transfected with FGFR3:TACC3 fusion vector, FGFR3 vector or empty plasmid vector. Proliferation, migration, colony formation and survival of these overexpressed cell lines were compared. Effect of pan-FGFR tyrosine kinase inhibitor JNJ-42165279 to same cellular mechanisms in these different overexpression cell lines was also assessed. Furthermore, downstream effects of FGFR3:TACC3 and FGFR3 expressing cells to inhibition and stimulation with fibroblast growth factor was analyzed at protein level.

In these experiments, FGFR3:TACC3 overexpressed cells showed increased proliferation and FGFR3 overexpressed cells decreased proliferation compared to the control cells. FGFR3 expressing cells had also lowered colony forming capability. Inhibition of FGFR in these overexpressing cells showed decrease of proliferation in fusion positive cells. Inhibition had no significant effects on other cellular mechanisms. Phosphorylation of FGFR was decreased by inhibition in both FGFR3:TACC3 and FGFR3 overexpressed cell lines.