{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:53:44Z","timestamp":1791478424293,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BIOMECA Consortium"},{"name":"Carrefour"},{"name":"Etoile de Martin"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ependymoma with <jats:italic>RELA<\/jats:italic> fusion has been defined as a novel entity of the revised World Health Organization 2016 classification of tumors of the central nervous system (CNS), characterized by fusion transcripts of the <jats:italic>RELA<\/jats:italic> gene and consequent pathological activation of the NFkB pathway. These tumors represent the majority of supratentorial ependymomas in children. The validation of diagnostic tools to identify this clinically relevant ependymoma entity is essential. Here, we have used interphase fluorescent <jats:italic>in situ<\/jats:italic> hybridization (FISH) for <jats:italic>C11orf95 <\/jats:italic>and <jats:italic>RELA<\/jats:italic>, immunohistochemistry (IHC) for p65\u2010RelA and the recently developed DNA methylation\u2010based classification besides conventional histopathology, and compared the precision of the methods in 40 supratentorial pediatric brain tumors diagnosed as ependymomas in the past years. Reverse transcription PCR (RT\u2010PCR) and RNA sequencing were performed to explore discordant cases. Furthermore, we integrated imaging and clinical features as additional layers of information. The concordance between nuclear RelA expression by IHC and <jats:italic>RELA<\/jats:italic> FISH was 100%. Concordance between IHC and DNA methylation profiling, and between FISH and DNA methylation profiling was also high (96.4% and 95.2%, respectively). Thirty\u2010four out of 40 (85%) cases were confirmed by integrated diagnoses as ependymal tumors, including 22 <jats:italic>RELA<\/jats:italic>\u2010fused ependymomas (71% of ependymal tumors), two <jats:italic>YAP1\u2010<\/jats:italic>fused ependymomas (6%), six non\u2010<jats:italic>RELA<\/jats:italic>\/non\u2010<jats:italic>YAP1<\/jats:italic> ependymomas (18%) and four ependymal\/subependymal mixed tumors (12%). Ependymal\/subependymal mixed tumors had an excellent clinical outcome despite the presence of histopathological signs of malignancy, suggesting that these tumors should not be diagnosed as classic ependymomas. DNA methylation profiling helped in the differential diagnosis of <jats:italic>RELA\u2010<\/jats:italic>fused ependymomas. IHC and FISH, which are available in the majority of pathology laboratories, are valuable tools to identify <jats:italic>RELA<\/jats:italic>\u2010fused ependymomas.<\/jats:p>","DOI":"10.1111\/bpa.12664","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T11:07:10Z","timestamp":1539688030000},"page":"325-335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Diagnostics of pediatric supratentorial RELA ependymomas: integration of information from histopathology, genetics, DNA methylation and imaging"],"prefix":"10.1111","volume":"29","author":[{"given":"M\u00e9lanie","family":"Pag\u00e8s","sequence":"first","affiliation":[{"name":"Department of Neuropathology Sainte\u2010Anne Hospital Paris France"},{"name":"Paris V Descartes University, Paris Cit\u00e9 Sorbonne Paris France"},{"name":"Institut National de la Sant\u00e9 et de la recherche M\u00e9dicale, INSERM Unit 1000 \u00ab Neuroimaging &amp; Psychiatrie \u00bb, Universit\u00e9 Paris Sud Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian W.","family":"Pajtler","sequence":"additional","affiliation":[{"name":"Hopp Children\u2019s Cancer Centre at the NCT (KiTZ) Heidelberg Germany"},{"name":"Division of Pediatric Neurooncology German Cancer Research Centre (DKFZ) and German Cancer Consortium (DKTK) Heidelberg Germany"},{"name":"Department of Hematology and Oncology Heidelberg University Hospital Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Puget","sequence":"additional","affiliation":[{"name":"Paris V Descartes University, Paris Cit\u00e9 Sorbonne Paris France"},{"name":"Department of Pediatric Neurosurgery Necker Enfants Malades Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Castel","sequence":"additional","affiliation":[{"name":"UMR8203 \u00ab Vectorologie et Th\u00e9rapeutiques Anticanc\u00e9reuses \u00bb Centre National de la Recherche Scientifique"},{"name":"D\u00e9partement de Canc\u00e9rologie de l\u2019Enfant et de l\u2019Adolescent Gustave Roussy, Univ. Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Boddaert","sequence":"additional","affiliation":[{"name":"Paris V Descartes University, Paris Cit\u00e9 Sorbonne Paris France"},{"name":"Radiology Department Necker Enfants Malades Hospital AP\u2010HP Paris France"},{"name":"Institut National de la Sant\u00e9 et de la recherche M\u00e9dicale, INSERM UMR 1163, Institut Imagine, and INSERM U1000 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnault","family":"Tauzi\u00e8de\u2010Espariat","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Sainte\u2010Anne Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Picot","sequence":"additional","affiliation":[{"name":"UMR8203 \u00ab Vectorologie et Th\u00e9rapeutiques Anticanc\u00e9reuses \u00bb Centre National de la Recherche Scientifique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Anne","family":"Debily","sequence":"additional","affiliation":[{"name":"UMR8203 \u00ab Vectorologie et Th\u00e9rapeutiques Anticanc\u00e9reuses \u00bb Centre National de la Recherche Scientifique"},{"name":"Universit\u00e9 d\u2019Evry\u2010Val d\u2019Essonne Evry France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Kool","sequence":"additional","affiliation":[{"name":"Hopp Children\u2019s Cancer Centre at the NCT (KiTZ) Heidelberg Germany"},{"name":"Division of Pediatric Neurooncology German Cancer Research Centre (DKFZ) and German Cancer Consortium (DKTK) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Capper","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health Berlin Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Centre (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Sainte\u2010Rose","sequence":"additional","affiliation":[{"name":"Paris V Descartes University, Paris Cit\u00e9 Sorbonne Paris France"},{"name":"Department of Pediatric Neurosurgery Necker Enfants Malades Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Chr\u00e9tien","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Sainte\u2010Anne Hospital Paris France"},{"name":"Paris V Descartes University, Paris Cit\u00e9 Sorbonne Paris France"},{"name":"Infection &amp; Epidemiology Department Human Histopathology and Animal Models Unit, Institut Pasteur Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Pfister","sequence":"additional","affiliation":[{"name":"Hopp Children\u2019s Cancer Centre at the NCT (KiTZ) Heidelberg Germany"},{"name":"Division of Pediatric Neurooncology German Cancer Research Centre (DKFZ) and German Cancer Consortium (DKTK) Heidelberg Germany"},{"name":"Department of Hematology and Oncology Heidelberg University Hospital Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Pietsch","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University of Bonn Medical Centre Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Grill","sequence":"additional","affiliation":[{"name":"UMR8203 \u00ab Vectorologie et Th\u00e9rapeutiques Anticanc\u00e9reuses \u00bb Centre National de la Recherche Scientifique"},{"name":"D\u00e9partement de Canc\u00e9rologie de l\u2019Enfant et de l\u2019Adolescent Gustave Roussy, Univ. 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