Alternative RNA Splicing in the Pathogenesis of GBM

Alternative splicing enables the generation of different proteins from a single gene, greatly increasing the use of genetic information. The resultant protein isoforms often have different biological properties effecting the phenotype of the cell in which it is expressed. Dysregulation of alternative splicing is a common occurrence in cancer and may lead to the formation of truncated or degraded proteins through the introduction of immature stop codons or nonsense mediated decay.  Increasing evidence indicates that cancer-associated splicing variants play an important role in tumor initiation and progression. In this review, we summarize the evidence supporting the relevance of alternative splicing in glioblastoma multiforme (GBM). Specifically, we focus on the role of alternative splicing in GBM pathogenesis with an emphasis on the effect of aberrant alternative splicing of FGFR, GLI-1, and EGFR. The significance of exploiting alternatively spliced isoforms as potential biomarkers which may contribute to the development of diagnostic and prognostic methods, in addition to serving as molecular targets in GBM, will be discussed.