Supratentorial ependymoma in childhood: more than just RELA or YAP

• DOI: 10.1007/s00401-020-02260-5
• Publication Date: 2021-01-22T05:05:39Z
• Authors: Valentina Zschernack; Stephanie T. Jünger; Martin Mynarek; Stefan Rutkowski; Maria Luisa Garre; Martin Ebinger; Marie Neu; Jörg Faber; Bernhard Erdlenbruch; Alexander Claviez; Stefan Bielack; Triantafyllia Brozou; Michael C. Frühwald; Evelyn Dörner; Verena Dreschmann; Annika Stock; Laszlo Solymosi; Jürgen Hench; Stephan Frank; Christian Vokuhl; Andreas Waha; Felipe Andreiuolo; Torsten Pietsch
• Keywords: Ependymoma; Oligodendroglial Tumor; Immunophenotyping; Fusion transcript

Abstract Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by presence either a C11orf95-RELA or YAP-MAMLD1 fusion, respectively. There is growing evidence that ependymomas without these genetic features exist. In this study, we report on 18 pediatric non- RELA/ YAP were systematically means their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis fusion transcripts Nanostring technology, RNA sequencing. Based upon histological immunohistochemical two main patterns identified— RELA -like ( n = 9) tanycytic 6). group histologically assigned to WHO grade III resembling -fused ependymomas, tumors lacked nuclear expression p65-RelA as surrogate marker for pathological activation NF-κB pathway. Three showed alternative C11orf95 fusions MAML2 NCOA1 . A methylation-based brain tumor classifier class “EP, -fusion”; others demonstrated no significant similarity score. Of group, 5/6 II. No gene detected. Methylation profiling did not show any association with an established class. We additionally identified astroblastoma-like both presented chromothripsis chromosome 22 but MN1 breaks according FISH analysis. They revealed novel events involving genes 22. One further polyploid cytogenetics was interpreted PFB had relation posterior fossa. Clinical follow-up available 16/18 patients. Patients relapse, while 2 patients died. Our data indicate addition discovered so far, at least more types tanycytic)