EPEN-11. ANALYSIS OF EXPRESSION OF YAP1, RELA, MAMLD1 AND FAM118B GENES IN PEDIATRIC EPENDYMOMA

Abstract

Ependymomas (EPN) are primary tumors in the central nervous system (CNS). In children, 90% of EPNs occur intracranial, with two-thirds being located in the posterior fossa (PF) and one-third within the supratentorial (ST) compartment. Despite the development of new molecular classifications and increasing understanding of the underlying EPN mechanisms, management and treatment remain challenging. We investigated the expression of genes involved in EPN molecular rearrangements (YAP1, RELA, MAMLD1 and FAM118B), in 27 EPN patients from Pediatric Oncology Institute - GRAACC, Brazil. Gene expression levels were quantified using qPCR. Molecular findings were correlated to clinicopathological characteristics of patients. Significant results were considered when p<0.005. Overall survival was significantly lower in patients with PF tumors than ST tumors (p=0.0109), and high YAP1 expression was related to worst overall survival (p=0.0488). ST tumors presented higher RELA expression than PF tumors (p=0.0089). Expression of YAP1 and FAM118B genes significantly correlated (r=0.917, p<0.0001). All investigated genes are partners in fusion genes recently described for EPN and the levels of expression observed were in agreement with findings in the literature. Additional studies are in progress to collaborate with the characterization of EPN genetics, once development of targeted therapies will require the understanding of tumor biology and its effect in the clinical outcomes. Based on recent molecular findings, and after the actualization of WHO classification of tumors of the CNS in 2016, it is becoming evident that, in the near future, histologic criteria alone might be insufficient to direct treatment, to predict outcomes and refine EPN treatment.