Evidence map›Paper›PMID 36916248›Full record

ArticleNeuro-oncology2023

Optimizing biomarkers for accurate ependymoma diagnosis, prognostication, and stratification within International Clinical Trials: A BIOMECA study.

Rebecca J Chapman, David R Ghasemi, Felipe Andreiuolo, Valentina Zschernack, Arnault Tauziede Espariat, Francesca R Buttarelli, Felice Giangaspero, Jacques Grill, Christine Haberler, Simon M L Paine and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.5field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Bridging pediatric and adult neuro-oncology: Insights into adolescents and young adults (AYA) central nervous system tumors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  3. ZFTA::YAP1-rearranged ependymoma: is still ZFTA or already YAP?Acta neuropathologica communications · 2026
    Article
  4. A brief history of ependymoma.Neuro-oncology · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 13 institutions in 6 countries.

Rebecca J ChapmanChildren's Brain Tumour Research Centre, University of Nottingham, Nottingham, UK.ORCID 0000-0001-8050-8426
David R GhasemiHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Felipe AndreiuoloDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Valentina ZschernackDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Arnault Tauziede EspariatDepartement de Neuropathologie, Hopital Sainte-Anne, Paris, France.
Francesca R ButtarelliDepartment of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
Felice GiangasperoDepartment of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
Jacques GrillINSERM Unit 981 and Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.ORCID 0000-0003-4773-3001
Christine HaberlerDivision of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0003-1016-0545
Simon M L PaineDepartment of Neuropathology, Nottingham University Hospital, Nottingham, UK.
Ian ScottDepartment of Neuropathology, Nottingham University Hospital, Nottingham, UK.
Thomas S JacquesDevelopmental Biology and Cancer Programme, UCL GOS Institute of Child Health, London, UK.
Martin SillHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Stefan PfisterHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
John-Paul KildayChildren's Brain Tumour Research Network (CBTRN), Royal Manchester Children's Hospital, Manchester, UK.ORCID 0000-0002-0539-215X
Pierre LeblondInstitute of Hematology and Pediatric Oncology (IHOPe), Leon Berard Comprehensive Cancer Center, Lyon, France.ORCID 0000-0002-7088-2614
Maura MassiminoPaediatric Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milano, Italy.
Hendrik WittHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Piergiorgio ModenaGenetics Unit, Pathology Department, Ospedale S. Anna, Como, Italy.
Pascale VarletDepartement de Neuropathologie, Hopital Sainte-Anne, Paris, France.
Torsten PietschDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Richard G GrundyChildren's Brain Tumour Research Centre, University of Nottingham, Nottingham, UK.
Kristian W PajtlerChildren's Brain Tumour Research Centre, University of Nottingham, Nottingham, UK.
Timothy A RitzmannChildren's Brain Tumour Research Centre, University of Nottingham, Nottingham, UK.ORCID 0000-0002-4438-6588
University of Nottingham · GBGerman Cancer Research Center · DEInserm · FRUniversity of Bonn · DEFondazione IRCCS Istituto Nazionale dei Tumori · ITGreat Ormond Street Hospital · GBHopp Children's Cancer Center Heidelberg · DEInstitut d’Hématologie et d’Oncologie Pédiatrique · FRIstituto Neurologico Mediterraneo · ITMedical University of Vienna · ATOspedale Sant'Anna · ITSapienza University of Rome · ITUniversity of Manchester · GB

Funding

Cancer Research UK
6 · The paper itself

Abstract

backgroundAccurate 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 "Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)" study.

methodsAcross 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.

resultsDNA 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 3 centers). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP-fused 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.

conclusionsWe 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.

Indexed as

EpendymomaHistonesAdolescentBiomarkersChildHumansIn Situ Hybridization, FluorescenceProspective StudiesTenascinBiomarkersHistonesTenascinbiomarkersbrain tumorsEpendymomaneuro-oncologypaediatric

Identifiers

PMID36916248
PMCPMC10547510
OpenAlexW4324104828

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.