Supratentorial ependymoma in childhood: more than just RELA or YAP

Medientyp: E-Artikel
Titel: Supratentorial ependymoma in childhood: more than just RELA or YAP
Beteiligte: Zschernack, Valentina; Jünger, Stephanie T.; Mynarek, Martin; Rutkowski, Stefan; Garre, Maria Luisa; Ebinger, Martin; Neu, Marie; Faber, Jörg; Erdlenbruch, Bernhard; Claviez, Alexander; Bielack, Stefan; Brozou, Triantafyllia; Frühwald, Michael C.; Dörner, Evelyn; Dreschmann, Verena; Stock, Annika; Solymosi, Laszlo; Hench, Jürgen; Frank, Stephan; Vokuhl, Christian; Waha, Andreas; Andreiuolo, Felipe; Pietsch, Torsten
Erschienen: Springer Science and Business Media LLC, 2021
Erschienen in: Acta Neuropathologica
Sprache: Englisch
DOI: 10.1007/s00401-020-02260-5
ISSN: 0001-6322; 1432-0533
Schlagwörter: Cellular and Molecular Neuroscience ; Neurology (clinical) ; Pathology and Forensic Medicine
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Beschreibung: <jats:title>Abstract</jats:title><jats:p>Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a <jats:italic>C11orf95-RELA</jats:italic> or a <jats:italic>YAP-MAMLD1</jats:italic> fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-<jats:italic>RELA/</jats:italic>non-<jats:italic>YAP</jats:italic> supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified—<jats:italic>RELA</jats:italic>-like (<jats:italic>n</jats:italic> = 9) and tanycytic ependymomas (<jats:italic>n</jats:italic> = 6). In the <jats:italic>RELA</jats:italic>-like group histologically assigned to WHO grade III and resembling <jats:italic>RELA</jats:italic>-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-κB pathway. Three tumors showed alternative <jats:italic>C11orf95</jats:italic> fusions to <jats:italic>MAML2</jats:italic> or <jats:italic>NCOA1</jats:italic>. A methylation-based brain tumor classifier assigned two <jats:italic>RELA</jats:italic>-like tumors to the methylation class “EP, <jats:italic>RELA</jats:italic>-fusion”; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked <jats:italic>MN1</jats:italic> breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patients with <jats:italic>RELA</jats:italic>-like ependymomas died. Our data indicate that in addition to ependymomas discovered so far, at least two more supratentorial ependymoma types (<jats:italic>RELA</jats:italic>-like and tanycytic) exist.</jats:p>

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