Transcriptome analysis and gene networks in a rare pediatric tumor

Abstract

Ependymoma, a rare pediatric tumor originating from ependymal cells located in the lining of ventricular surfaces in the brain, presents great challenges in treatment despite advances in neurosurgical techniques. In order to identify new molecular biomarkers that could improve clinical management and outcomes, we have used RNA-seq to profile the Whole Transcriptome of three ependymoma samples and one normal control brain tissue, producing a total of 2.5 Gigabases of sequencing data. Different protein-coding gene databases were interrogated for known annotated genes to calculate RPKM and Fold Changes (FGs) for each clustered gene. Using this approach, we were able to identify Differentially Expressed Genes (DEGs) in ependymomas. KEGG pathways and Gene Ontology (GO) categories enriched in the DEGs were analyzed using Enrichr, and protein interaction networks were then built using MetaCore™. Thirty differentially expressed protein-coding genes associated with neurogenesis were identified by TaqMan Real-Time PCR, 17 of these showing statistically significant differential expression. Based on these results, we have identified IGF-2 as highly over-expressed in ependymomas and that this is due to loss of DNA methylation in its promoter region. In conclusion, we believe that some of these genes, specially IGF-2, may be of clinical importance, opening new avenues for disease management and new therapies.