DNA methylation and transcriptomic alterations define distinct groups in pediatric spinal ependymoma. (12th October 2019)

• Record Type: Journal Article
• Authors: Ahmad, Omar; Chapman, Rebecca; Storer, Lisa; Luo, Li; Resar, Linda; Cohen, Kenneth; Grundy, Richard; Lourdusamy, Anbarasu
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 4
• Page Start: iv6
• Page End: iv6
• Publication Date: 2019-10-12
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz167.025
• Languages: English
• ISSNs: 1522-8517

Abstract

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.