Heterogeneous , , , and Gene Expression Profiles in Primary GBM: No Association with Patient Survival.

BACKGROUND

The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial.

METHODS

We investigated the RNA gene expression profile of epidermal growth factor receptor (), cyclin-dependent kinase 4 (), murine doble minute 4 (), and platelet derived growth factor receptor alpha () in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in and were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied.

RESULTS

At the RNA level, was the most frequently overexpressed gene (90%) followed by (58%) and (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with gene expression levels. In turn, intragenic deletions were found in 39 patients (47%), including (46%) in association with (4%), (2%) or other deletions (3%) and deletion of exons 8-9 was found in only two tumors (2%).

CONCLUSIONS

Overall, none of the gene expression profiles and/or intragenic deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.