{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:53:28Z","timestamp":1791478408634,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001273","name":"CHILDREN with CANCER UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001273","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health Research Funded Academic Clinical Lecturer and Fighting Ependymoma"},{"DOI":"10.13039\/501100004350","name":"Studienstiftung des Deutschen Volkes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004350","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate identification of brain tumor molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European \u201cBiomarkers of Ependymoma in Children and Adolescents (BIOMECA)\u201d study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Across 6 European BIOMECA laboratories, we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via fluorescent in situ hybridization (FISH) and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DNA Methylation profiling classified 65.3% (n = 96\/147) of cases as EPN-PFA and 15% (n = 22\/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99%\u2013100% across 3 centers). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP\u2014fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-center concordance and low sensitivity and specificity while MIP, MLPA, and DNA methylation-based approaches demonstrated greater accuracy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q, and CDKN2A loss while FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noad055","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T15:09:57Z","timestamp":1678720197000},"page":"1871-1882","source":"Crossref","is-referenced-by-count":17,"title":["Optimizing biomarkers for accurate ependymoma diagnosis, prognostication, and stratification within International Clinical Trials: A BIOMECA study"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8050-8426","authenticated-orcid":false,"given":"Rebecca J","family":"Chapman","sequence":"first","affiliation":[{"name":"Children\u2019s Brain Tumour Research Centre, University of Nottingham , Nottingham , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Ghasemi","sequence":"additional","affiliation":[{"name":"Hopp Children\u2019s Cancer Center Heidelberg (KiTZ) , Heidelberg , Germany"},{"name":"Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK) , Heidelberg , Germany"},{"name":"Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital , Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Andreiuolo","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn , Bonn, Germany"},{"name":"Instituto Estadual do Cerebro Paulo Niemeyer , Rio de Janerio , Brazil"},{"name":"IDOR Institute , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Zschernack","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn , Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnault Tauziede","family":"Espariat","sequence":"additional","affiliation":[{"name":"Departement de Neuropathologie, Hopital Sainte-Anne , Paris , France"},{"name":"INSERM Unit 981 and Department of Pediatric and Adolescent Oncology , Gustave Roussy, Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca R","family":"Buttarelli","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome , Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Giangaspero","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome , Rome, Italy"},{"name":"IRCCS Neuromed , Pozzilli , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-3001","authenticated-orcid":false,"given":"Jacques","family":"Grill","sequence":"additional","affiliation":[{"name":"INSERM Unit 981 and Department of Pediatric and Adolescent Oncology , Gustave Roussy, Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-0545","authenticated-orcid":false,"given":"Christine","family":"Haberler","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M L","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Nottingham University Hospital , Nottingham , 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Pediatric Neuro-oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK) , Heidelberg , Germany"},{"name":"Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital , Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0539-215X","authenticated-orcid":false,"given":"John-Paul","family":"Kilday","sequence":"additional","affiliation":[{"name":"Children\u2019s Brain Tumour Research Network (CBTRN), Royal Manchester Children\u2019s Hospital , Manchester , UK"},{"name":"The Centre for Paediatric, Teenage and Young Adult Cancer, Institute of Cancer Sciences, University of Manchester , Manchester , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-2614","authenticated-orcid":false,"given":"Pierre","family":"Leblond","sequence":"additional","affiliation":[{"name":"Institute of 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Modena","sequence":"additional","affiliation":[{"name":"Genetics Unit, Pathology Department, Ospedale S. 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