Evidence map›Paper›PMID 28733933›Full record

ArticleActa neuropathologica2017

Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.

Pooja Panwalkar, Jonathan Clark, Vijay Ramaswamy, Debra Hawes, Fusheng Yang, Christopher Dunham, Stephen Yip, Juliette Hukin, Yilun Sun, Matthew J Schipper and 30 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05151718 (Ependymomics), which is not on this map. Cited by 132 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 2 pooled it
11.2field-weighted citation impact, top 1% 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.

NCT05151718 recruitingnot on this mapstarted 2021, after this paper: background citation

Ependymomics: Multiomic Approach to Radioresistance of Ependymomas in Children and Adolescents

TypeobservationalSponsorInstitut Claudius RegaudRan2021 to 2026Enrolled370ConditionsEpendymoma of Brain, Pediatric Solid Tumor
3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 243 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Review
  8. "Updates on diagnostic and prognostic molecular biomarkers of CNS tumors".Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  9. Article
  10. A brief history of ependymoma.Neuro-oncology · 2026
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. H3 K27M mutation in rosette-forming glioneuronal tumors: a potential diagnostic pitfall.Virchows Archiv : an international journal of pathology · 2025
    Article
  19. Review
  20. Review

72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors at 20 institutions in 4 countries.

Pooja PanwalkarDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
Jonathan ClarkDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
Vijay RamaswamyDivision of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Debra HawesDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, 4650 Sunset Boulevard, MS #43, Los Angeles, CA, 90027, USA.
Fusheng YangDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, 4650 Sunset Boulevard, MS #43, Los Angeles, CA, 90027, USA.
Christopher DunhamDivision of Anatomic Pathology, British Columbia Children's Hospital, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada.
Stephen YipDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T1Z3, BC, Canada.
Juliette HukinDivisions of Neurology and Hematology and Oncology, Children's and Women's Health Centre of B.C, University of British Columbia, Vancouver, BC, V6H 3N1, Canada.
Yilun SunDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Matthew J SchipperDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Lukas ChavezDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ashley MargolDepartment of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA, 90027, USA.
Melike PekmezciDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Chan ChungDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
Adam BandaDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
Jill M BaylissDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
Sarah J CurryDivision of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Mariarita SantiDepartment of Anatomic Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Fausto J RodriguezDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Matija SnuderlDepartment of Pathology, New York University, New York, NY, USA.
Matthias A KarajannisDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Amanda M SaratsisDepartment of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Craig M HorbinskiDepartment of Pathology and Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Anne-Sophie CarretDivision of Hematology-Oncology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
Beverly WilsonDivision of Pediatric Hematology/Oncology, Stollery Children's Hospital, University of Alberta, Edmonton, AB, T2W3N2, Canada.
Donna JohnstonDivision of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
Lucie Lafay-CousinDivision of Pediatric Hematology/Oncology, Alberta Children's Hospital, Calgary, AB, T3B6A8, Canada.
Shayna ZelcerDivision of Pediatric Hematology/Oncology, London Health Sciences Center, Children's Hospital, London, ON, N6A5A5, Canada.
David EisenstatDepartment of Pediatrics and Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Marianna SilvaKingston General Hospital, Kingston, ON, Canada.
Katrin ScheinemannDepartment of Pediatrics, McMaster University, Hamilton, ON, Canada.
Nada JabadoDepartment of Pediatrics, McGill University, Montreal, QC, H3Z2Z3, Canada.
P Daniel McNeelyDivision of Neonatal Pediatrics, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
Marcel KoolDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stefan M PfisterDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael D TaylorDivision of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Cynthia HawkinsPediatric Laboratory Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Andrey KorshunovDepartment of Neuropathology, German Cancer Research Center (DKFZ), University Hospital Heidelberg and CCU Neuropathology, Heidelberg, Germany.
Alexander R JudkinsDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, 4650 Sunset Boulevard, MS #43, Los Angeles, CA, 90027, USA. ajudkins@chla.usc.edu.
Sriram VennetiDepartment of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA. svenneti@med.umich.edu.
University of Michigan · USChildren's Hospital of Los Angeles · USHospital for Sick Children · CANorthwestern University · USUniversity of Alberta · CAUniversity of British Columbia · CAUniversity of Southern California · USUniversity of Toronto · CAAlberta Children's Hospital · CABC Children's Hospital · CAChildren's Hospital of Philadelphia · USDalhousie University · CADeutschen Konsortium für Translationale Krebsforschung · DEGerman Cancer Research Center · DEHeidelberg University · DEJohns Hopkins University · USKingston General Hospital · CALondon Health Sciences Centre · CAMcGill University · CAMcMaster University · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
University of Michigan Postbaccalaureate Research Education Program (UM PREP)R25GM086262 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALLEN, BENJAMIN · 2009 to 2024
$6.1M
Investigation of Histone H3 Post-Translational Modifications in Pediatric Brainstem GliomaK08NS097624 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SARATSIS, AMANDA MUHS · 2016 to 2022
$918k
Unraveling glutamine metabolism in gliomas by PET imaging and biochemical methodsK08CA181475 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VENNETI, SRIRAM · 2014 to 2018
$701k
NCATS NIH HHS UL1 TR001422NCI NIH HHS K08 CA181475NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA046592NIGMS NIH HHS R25 GM086262NIGMS NIH HHS T32 GM007315NINDS NIH HHS K08 NS097624
6 · The paper itself

Abstract

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

Indexed as

ChildChild, PreschoolDisease-Free SurvivalEpendymomaFemaleHumansInfantInfratentorial NeoplasmsJumonji Domain-Containing Histone DemethylasesMalePrognosisRegistriesSurvival RateJumonji Domain-Containing Histone DemethylasesKDM6B protein, humanChildhood ependymomaEpigeneticsH3K27me3Molecular subgrouping

Identifiers

PMID28733933
PMCPMC5647236
OpenAlexW2737623654

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.