Abstract
Paediatric spinal ependymomas are important, albeit uncommon, malignant central nervous system tumours. Unlike adults, 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 metastases. The clinical and molecular factors underlying these differences remain poorly characterized. We analyzed spinal ependymoma (SEPN) tumour samples from 27 paediatric patients (female: 11, male: 15; age range: 4–18 years) using genome-wide DNA methylation profiling, copy-number analysis, as well as transcriptome profiling. Using DNA methylation profiles, two distinct unsupervised consensus-clustering approaches, hierarchical clustering and non-negative matrix factorization reliably identified two subgroups. These subgroups were designated as Myxopapillary ependymomas (SP-MPE) and spinal ependymomas (SP-EPN) based on the online Classifier tool (MNP2.0). The genome-wide copy-number analysis showed differences in numbers and pattern of copy-number alterations between these groups. The gain of chromosome 20 (39%) followed by loss of chromosomes 6 (28%), 10 (28%), and 13 (28%) were detected in the SP-MPE group, whereas loss of chromosome 22 was frequent (60%) in the SP-EPN group. Transcriptomics analysis showed that genes associated with oxidative phosphorylation, TCA cycle components, electron transport, and Interferon-gamma production characterize the SP-MPE group whereas potassium ion import and regulation of astrocyte differentiation characterize the SP-EPN group. Western blot analysis validated the increased protein expression of oxidative phosphorylation complexes in SP-MPE. With this study, we provide a foundation for further molecular characterization of pediatric SEPN subgroups. Our results suggest that mitochondrial oxidative phosphorylation may drive the regulation of energy metabolism of SP-MPE tumours.