Zschernack, Valentina, Junger, Stephanie T., Mynarek, Martin, Rutkowski, Stefan, Garre, Maria Luisa, Ebinger, Martin ORCID: 0000-0002-4229-8058, Neu, Marie, Faber, Joerg, Erdlenbruch, Bernhard, Claviez, Alexander, Bielack, Stefan, Brozou, Triantafyllia, Fruehwald, Michael C., Doerner, Evelyn, Dreschmann, Verena, Stock, Annika ORCID: 0000-0003-0148-4652, Solymosi, Laszlo ORCID: 0000-0001-9647-8647, Hench, Juergen, Frank, Stephan, Vokuhl, Christian, Waha, Andreas, Andreiuolo, Felipe and Pietsch, Torsten (2021). Supratentorial ependymoma in childhood: more than just RELA or YAP. Acta Neuropathol., 141 (3). S. 455 - 467. NEW YORK: SPRINGER. ISSN 1432-0533

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Abstract

Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP 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-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-kappa B pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class EP, RELA-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 MN1 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 RELA-like ependymomas died. Our data indicate that in addition to ependymomas discovered so far, at least two more supratentorial ependymoma types (RELA-like and tanycytic) exist.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zschernack, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Junger, Stephanie T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mynarek, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rutkowski, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garre, Maria LuisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebinger, MartinUNSPECIFIEDorcid.org/0000-0002-4229-8058UNSPECIFIED
Neu, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faber, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erdlenbruch, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claviez, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bielack, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brozou, TriantafylliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fruehwald, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doerner, EvelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dreschmann, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stock, AnnikaUNSPECIFIEDorcid.org/0000-0003-0148-4652UNSPECIFIED
Solymosi, LaszloUNSPECIFIEDorcid.org/0000-0001-9647-8647UNSPECIFIED
Hench, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frank, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vokuhl, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waha, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andreiuolo, FelipeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pietsch, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-603656
DOI: 10.1007/s00401-020-02260-5
Journal or Publication Title: Acta Neuropathol.
Volume: 141
Number: 3
Page Range: S. 455 - 467
Date: 2021
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-0533
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Clinical Neurology; Neurosciences; PathologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60365

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