Abstract
Under the auspices of the World Health Organization Classification of CNS Tumors (5th Edition), supratentorial ependymomas are divided into 2 main molecular groups, comprising tumors that are either ZFTA- or YAP1-fused with the majority harboring ZFTA::RELA fusion. ZFTA-rearranged ependymomas with non-canonical 3´ fusion partners have significant clinical, radiological, and histopathological variability. We report a 5-year-old girl with a left frontal lobe tumor harboring a ZFTA::YAP1 fusion. The patient presented with recurrent absence episodes aggravating to epileptic seizures. The histological appearance of the tumor was inconclusive and shared morphological features of ependymal and glioneuronal neoplasms. Despite the nominal presence of a ZFTA alteration typically associated with aggressive ependymal tumors, the lesion demonstrated prolonged indolent biological behavior. Gene expression assay revealed paradoxical activation of YAP/TAZ signaling and signature unambiguously correspondent to YAP1-activated ependymoma. To our knowledge, this is the first case report demonstrating the molecular background of ZFTA::YAP1-rearranged ependymoma. The case denies the binary classification of supratentorial ependymomas into ZFTA and YAP1 subtypes based entirely on the identity of 5' partner gene involved in the rearrangement. The findings elaborate the concept of molecular pathogenesis for YAP1-rearranged tumors.