Abstract Ependymomas (EPN) are heterogenous tumours occurring in children and adults. They are believed to arise from the ependymal cells and occur in the three major compartments of the central nervous system (spine (SP), posterior fossa (PF), supratentorial (ST)). EPN are further subdivided into molecular types displaying distinct epigenomic profiles and clinical characteristics. Despite advancements in diagnostics and tumour characterization, the prognosis for EPN remains variable and is largely dependent on the extent of tumour resection. Thus, there is a high need for targeted adjuvant therapy. Focusing on integrated proteomic analyses, the goal of this study was to identify tumour type specific targetable proteins and putative biomarkers to enhance the efficient diagnosis and therapy of EPN. Histomorphology, DNA-methylation-, proteome- and phosphoproteome data was assessed from formalin-fixed paraffin-embedded (FFPE) samples of primary human EPN. Molecular diagnosis was verified based on DNA-methylation data using the brain tumour classifier (V12.8, classifier score 0.8). Proteome data were generated with label-free quantification and data dependent acquisition of proteins using mass spectrometry. Established epigenomic EPN types were reflected in our main cohort (n = 196 EPN with MPE: n = 41, SP-EPN: n = 31, SP-EPN-MYCN: n = 8, SP-SE: n = 8, ST-SE: n = 12, PFA1: n = 19, PFA2: n = 10, PFB: n = 22, PF-SE: n = 18, EPN-YAP: n = 7, EPN-ZFTA: n = 20). Matched protein samples revealed that EPN types were reflected on the proteome level with subependymomas (SE) of all compartments showing high similarity. SNF clustering integrating both data modalities revealed stable clustering of EPN types in CNS compartments. EPN types displayed distinct protein patterns allowing for detection of putative markers and targetable proteins. Results were further confirmed in a validation cohort (n = 73). Preliminary findings of the phosphoproteome analysis showed high EPN heterogeneity and partial overlap with known methylome subtypes. In-depth integrative analyses are ongoing and will help to identify EPN type specific dysregulated biological pathways, biomarkers and treatment targets.
Gocke et al. (Fri,) studied this question.