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000274243 1001_ $$00000-0001-8050-8426$$aChapman, Rebecca J$$b0
000274243 245__ $$aOptimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within International Clinical Trials: A BIOMECA study.
000274243 260__ $$aOxford$$bOxford Univ. Press$$c2023
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000274243 500__ $$a#LA:B062# / 2023 Oct 3;25(10):1871-1882
000274243 520__ $$aAccurate identification of brain tumour molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European 'Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)' study.Across six European BIOMECA laboratories we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via FISH and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH.DNA Methylation profiling classified 65.3% (n=96/147) of cases as EPN-PFA and 15% (n=22/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99-100% across three centres). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP1- fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-centre concordance and low sensitivity and specificity whilst MIP, MLPA and DNA methylation-based approaches demonstrated greater accuracy.We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q and CDKN2A loss whilst FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches.
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000274243 650_7 $$2Other$$aEpendymoma
000274243 650_7 $$2Other$$abiomarkers
000274243 650_7 $$2Other$$abrain tumours
000274243 650_7 $$2Other$$aneuro-oncology
000274243 650_7 $$2Other$$apaediatric
000274243 7001_ $$0P:(DE-HGF)0$$aGhasemi, David R$$b1
000274243 7001_ $$aAndreiuolo, Felipe$$b2
000274243 7001_ $$aZschernack, Valentina$$b3
000274243 7001_ $$aTauziede Espariat, Arnault$$b4
000274243 7001_ $$aButtarelli, Francesca R$$b5
000274243 7001_ $$aGiangaspero, Felice$$b6
000274243 7001_ $$00000-0003-4773-3001$$aGrill, Jacques$$b7
000274243 7001_ $$00000-0003-1016-0545$$aHaberler, Christine$$b8
000274243 7001_ $$aPaine, Simon M L$$b9
000274243 7001_ $$aScott, Ian$$b10
000274243 7001_ $$aJacques, Thomas S$$b11
000274243 7001_ $$aSill, Martin$$b12
000274243 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b13$$udkfz
000274243 7001_ $$00000-0002-0539-215X$$aKilday, John-Paul$$b14
000274243 7001_ $$00000-0002-7088-2614$$aLeblond, Pierre$$b15
000274243 7001_ $$aMassimino, Maura$$b16
000274243 7001_ $$0P:(DE-He78)046fd145f1008f83f6236580727bbc0f$$aWitt, Hendrik$$b17
000274243 7001_ $$aModena, Piergiorgio$$b18
000274243 7001_ $$aVarlet, Pascale$$b19
000274243 7001_ $$aPietsch, Torsten$$b20
000274243 7001_ $$aGrundy, Richard G$$b21
000274243 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b22$$eLast author$$udkfz
000274243 7001_ $$00000-0002-4438-6588$$aRitzmann, Timothy A$$b23
000274243 7001_ $$aChildhood, Biomarkers of Ependymoma in$$b24
000274243 7001_ $$aAdolescence$$b25$$eCollaboration Author
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