Abstract
In contrast, compared to adults, spinal ependymomas (SEPN) are less common in childhood and adolescents. Children with these tumours are likely to experience a more aggressive disease course, with a higher rate of local failure, and a higher rate of metastasis. Presently the molecular basis of SEPN is poorly characterized. Therefore, we have analyzed 29 SEPN tumour samples from pediatric patients (female: 11, male: 15; age range: 4 – 21 years) and performed DNA methylation (n=28) and transcriptome profiling (n=29). Unsupervised analysis of methylation data reliably separated these tumours into two distinct groups: one group covering all myxopapillary ependymomas (MPE) and a second group dominated by grade II SPENs (SP-EPN). We identified 242 differentially methylated regions between these two groups, of which 56% showed high methylation levels in MPE, including 22 regions localized on chromosome 6. Genome-wide copy number analysis using methylation data showed differences in numbers and pattern of DNA copy number alterations between these groups. Gain of chromosome 20 (39%) followed by loss of chromosomes 6 (28%), 10 (28%), and 13 (28%) were detected in the MPE group, whereas loss of chromosome 22 was frequent (60%) in the SP-EPN group. Transcriptomic analysis showed that genes associated with oxidative phosphorylation, TCA cycle components, electron transport, and Interferon-gamma production characterize the MPE group whereas potassium ion import and regulation of astrocyte differentiation characterize the SP-EPN group. Taken together, this data suggest that mitochondrial oxidative phosphorylation may drive the regulation of energy metabolism of MPE tumours.