gms | German Medical Science

Objective: Fibroblast growth factors (FGFs) and its receptors are known to play a role in glioblastomas and are targets for chemotherapy like tyrosine-kinase inhibitors (TKI) already. Among the FGF-receptor (FGFR) genes 1-4, FGFR1, 2 and 3 express alternative splice isoforms b and c. Focus of glioma research has been mainly on FGFR1 and 2. Although FGFR3 is known to entail oncogenic mechanisms through the PI3K/AKT-signaling pathway, only few investigations of its particular role in gliomas have been performed and especially the FGFR3c and 3b alternative splice isoforms haven’t been taken into account so far. We here analyzed FGF-receptor expression of different isoforms in different glioma patient cohorts in order to find indications of altered expression patterns dependent on isoform and tumor type.

Method: 70 tumor samples from low- and high-grade glioma patients with and without treatment were classified into seven subgroups (WHO grade II, III, secondary glioblastoma ± chemotherapy, primary glioblastoma ± chemotherapy, peritumoral tissue). After mRNA isolation cDNA was synthesized and quantitative real-time PCR was performed (Qiagen Rotor-Gene Q cycler) assessing the expression of different FGFR isoforms. SDHA was used as a housekeeping gene.

Results: Expression of the FGF-R3IIIc isoform expression in all investigated glioma groups (mean ± SEM: 10.14 ± 2.26) was reduced compared to control tissue (mean ± SEM: 25.90 ± 5.40). Corroborating previously published data, expression of the FGF-R2IIIc was increased in anaplastic and diffuse gliomas compared to control brain tissue (mean ± SEM: 2.83 ± 0.90) with significant elevations in WHO grade II astrocytomas (mean ± SEM:11.02 ± 2.03). In addition, broad expression profiles of all other FGRR isoforms and changes in affinity of the numerous FGFs dependent on WHO grade and treatment are going to be processed.

Conclusions: In a first step we here analyzed two FGFR isoforms. As described in published data, FGFR2 isoform b, was found higher expressed in lower grade gliomas and control tissue than in glioblastomas indicating a possible affiliation to the proneural subgroup or a tumor suppressive effect. These preliminary data suggest that FGF-R3IIIc has the reverse effect. Currently we are running investigations of further FGFR isoforms and especially of the FGFR3IIIb in order to see if expression changes of the alternative spliced isoforms in correlation with grades of malignancy in gliomas prove true.