Bioinformatics Analysis of Recurrent Deletion Regions in Neuroblastoma

Abstract

Neuroblastoma (NB) is the most common extra-cranial solid tumor in childhood. Very few genes in recurrent deletion regions have been identified as tumor suppressors for NB, and interactions among proteins encoded by genes in these regions have been overlooked. This study aims to identify possible tumor suppressor genes located within regions commonly deleted in NB tumors and to show possible interaction network of proteins encoded by genes in these regions by bioinformatics analysis. The genes localized in the recurrent deletion regions were identified using the Ensembl BioMart web-tool. GSE1824 microarray dataset was analyzed to determine downregulated differently expressed genes (dDEGs) selected from deletion regions using Orange Canvas software. The DAVID v6.8 tool and Reactome database were used to perform gene ontology and pathway enrichment analysis, respectively. The protein-protein interaction (PPI) network and sub-module analysis were conducted by STRING database and Cytoscape plugin MCODE software, respectively. Copy number variation status and mutations of hub genes were examined in TARGET neuroblastoma dataset using UCSC Xena platform. Biological processes of genes were specific to chromosomes. The 219 genes selected from these regions were found to be downregulated. A PPI network was constructed for dDEGs. Copy number losses and mutations were observed for hub genes. Hub genes identified in the current study may act as tumor suppressors in NB tumorigenesis. Disruption of protein-protein interaction network consisting of proteins encoded by genes on various recurrent deletion regions may give rise to NB by interrupting gene regulatory network orchestrating neural crest formation.