EPND-06. IDENTIFICATION OF DISTINCT MOLECULAR CHARACTERISTICS IN PEDIATRIC SPINAL EPENDYMOMA

Pediatric spinal ependymomas (pSP) are exceedingly rare central nervous system (CNS) tumors. Children with these tumours are likely to experience a more aggressive disease course, with a higher rate of local failure following treatment, and a higher rate of CNS metastasis, compared to adults. Because these tumours are uncommon, the molecular basis of pSP is poorly characterized. Microarray analysis of 66 pediatric ependymomas showed distinct expression patterns and detected up-regulation of several genes involved in development-related processes for spinal tumours. In addition, multiple biological processes that are less known for their involvement in pSP, oxidative phosphorylation, cellular respiration, electron transport, and cofactor metabolic process were also detected. When we compared the expression profiles of pSP to adult spinal ependymomas (aSP), we found a very low number of differentially expressed genes (12.5%) shared between pSP and aSP. Analysis of microRNA (miRNA) expression arrays on an overlapping cohort of 49 patients showed that six miRNAs (miR-196a, miR-27b, miR-23b, miR-144*, and miR-10a and 10b) were up-regulated and four (miR-26a, and miR-885-5p, miR-124, and miR-153) were down-regulated in pSP. The integrative miRNA-mRNA network and predicted miRNA target analysis revealed that the miR-23–27 cluster (miR23b/miR27b) coordinately repressed expression of cell differentiation genes (ACVR1C, CBFA2T3, GPSM1, and PKDCC), and the miR-10 family (miR10a/10b) that reside within the Hox clusters of developmental regulators, repressed expression of CAM2, HDAC4, IL1RAPL1, and MTSS1L. Furthermore, these miRNA-mRNA interactions were not detected in other cancers when we conducted the TCGA data analysis across ten different cancer types. Further investigation of gene expression and DNA methylation profiles in a larger cohort of pediatric ependymomas is on going, and will establish specific molecular characteristics of pSP. The identification of these candidate genes/miRNAs provides an evidence-based rationale for functional studies that will help to interrogate the initiation and progression of pSP.