A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas.

ABSTRACT: Ependymomas (EPN) are rare central nervous system tumors that account for approximately 10% of intracranial tumors in children and 4% in adults. Despite their clinical and molecular heterogeneity, spanning supratentorial, posterior fossa, and spinal subtypes, treatment remains limited to surgery and radiotherapy, with chemotherapy offering minimal benefit. Here, we performed transcriptomic analysis of 370 human ependymoma samples and identified two distinct molecular subgroups: EPN-E1 and EPN-E2. The EPN-E1 cluster is enriched for supratentorial tumors harboring ZFTA-RELA fusions (ZFTA-RELA^fus), which occur in over 70% of cases and are associated with poor prognosis. To identify targeted therapies for this aggressive subtype, we validated a ZFTA-RELA^fus mouse model th

SUBMITTER: Chan M 

PROVIDER: S-EPMC12912970 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature