Helm, Bryan R.Zhan, XiaohuiPandya, Pankita H.Murray, Mary E.Pollok, Karen E.Renbarger, Jamie L.Ferguson, Michael J.Han, ZhiNi, DongZhang, JieHuang, Kun2020-02-252020-02-252019-08-30Helm, B. R., Zhan, X., Pandya, P. H., Murray, M. E., Pollok, K. E., Renbarger, J. L., Ferguson, M. J., Han, Z., Ni, D., Zhang, J., & Huang, K. (2019). Gene Co-Expression Networks Restructured Gene Fusion in Rhabdomyosarcoma Cancers. Genes, 10(9), 665. https://doi.org/10.3390/genes10090665https://hdl.handle.net/1805/22142Rhabdomyosarcoma is subclassified by the presence or absence of a recurrent chromosome translocation that fuses the FOXO1 and PAX3 or PAX7 genes. The fusion protein (FOXO1-PAX3/7) retains both binding domains and becomes a novel and potent transcriptional regulator in rhabdomyosarcoma subtypes. Many studies have characterized and integrated genomic, transcriptomic, and epigenomic differences among rhabdomyosarcoma subtypes that contain the FOXO1-PAX3/7 gene fusion and those that do not; however, few investigations have investigated how gene co-expression networks are altered by FOXO1-PAX3/7. Although transcriptional data offer insight into one level of functional regulation, gene co-expression networks have the potential to identify biological interactions and pathways that underpin oncogenesis and tumorigenicity. Thus, we examined gene co-expression networks for rhabdomyosarcoma that were FOXO1-PAX3 positive, FOXO1-PAX7 positive, or fusion negative. Gene co-expression networks were mined using local maximum Quasi-Clique Merger (lmQCM) and analyzed for co-expression differences among rhabdomyosarcoma subtypes. This analysis observed 41 co-expression modules that were shared between fusion negative and positive samples, of which 17/41 showed significant up- or down-regulation in respect to fusion status. Fusion positive and negative rhabdomyosarcoma showed differing modularity of co-expression networks with fusion negative (n = 109) having significantly more individual modules than fusion positive (n = 53). Subsequent analysis of gene co-expression networks for PAX3 and PAX7 type fusions observed 17/53 were differentially expressed between the two subtypes. Gene list enrichment analysis found that gene ontology terms were poorly matched with biological processes and molecular function for most co-expression modules identified in this study; however, co-expressed modules were frequently localized to cytobands on chromosomes 8 and 11. Overall, we observed substantial restructuring of co-expression networks relative to fusion status and fusion type in rhabdomyosarcoma and identified previously overlooked genes and pathways that may be targeted in this pernicious disease.en-USAttribution 4.0 InternationalCopy number variationGene co-expression analysisGene fusionQuasi-clique mergerRhabdomyosarcomaArticle