Evidence map›Paper›PMID 25200322›Full record

ArticleActa neuropathologica2014

A sensitive and specific histopathologic prognostic marker for H3F3A K27M mutant pediatric glioblastomas.

Sriram Venneti, Mariarita Santi, Michelle Madden Felicella, Dmitry Yarilin, Joanna J Phillips, Lisa M Sullivan, Daniel Martinez, Arie Perry, Peter W Lewis, Craig B Thompson and 1 more

Abstract read
In one paragraph

Article in Acta neuropathologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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

73 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Molecular features in gangliogliomas: a systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Pooled it
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  4. Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas.Archives of pathology & laboratory medicine · 2022
    Guideline
  5. Pooled it
  6. Trial
  7. Review
  8. Article
  9. Article
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  14. Molecular and Pathological Features of Paediatric High-Grade Gliomas.International journal of molecular sciences · 2024
    Review
  15. Article
  16. Article
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  19. Review
  20. Article

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

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

11 authors.

Sriram VennetiCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, 10065, USA, vennetis@mskcc.org.
Mariarita Santi
Michelle Madden Felicella
Dmitry Yarilin
Joanna J Phillips
Lisa M Sullivan
Daniel Martinez
Arie Perry
Peter W Lewis
Craig B Thompson
Alexander R Judkins

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Tissue CoreP50CA097257 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2002 to 2026
$57.4M
Role of IDH Mutations in Acute Myeloid MalignanciesR01CA168802 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI THOMPSON, CRAIG B · 2013 to 2017
$1.8M
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
NCI NIH HHS K08 CA181475NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA097257NCI NIH HHS R01 CA168802NCI NIH HHS R01CA168802
6 · The paper itself

Abstract

Pediatric glioblastomas (GBM) are highly aggressive and lethal tumors. Recent sequencing studies have shown that ~30 % of pediatric GBM and ~80 % of diffuse intrinsic pontine gliomas show K27M mutations in the H3F3A gene, a variant encoding histone H3.3. H3F3A K27M mutations lead to global reduction in H3K27me3. Our goal was to develop biomarkers for the histopathologic detection of these tumors. Therefore, we evaluated the utility of measuring H3K27me3 global reduction as a histopathologic and prognostic biomarker and tested an antibody directed specifically against the H3.3 K27M mutation in 290 samples. The study cohort included 203 pediatric (including 38 pediatric high-grade astrocytomas) and 38 adult brain tumors of various subtypes and grades and 49 non-neoplastic reactive brain tissues. Detection of H3.3 K27M by immunohistochemistry showed 100 % sensitivity and specificity and was superior to global reduction in H3K27me3 as a biomarker in diagnosing H3F3A K27M mutations. Moreover, cases that stained positive for H3.3 K27M showed a significantly poor prognosis compared to corresponding negative tumors. These results suggest that immunohistochemical detection of H3.3 K27M is a sensitive and specific surrogate for the H3F3A K27M mutation and defines a prognostically poor subset of pediatric GBM.

Indexed as

AdolescentAdultBrain NeoplasmsChildChild, PreschoolCohort StudiesDNA Mutational AnalysisFemaleGlioblastomaHistonesHumansInfant, NewbornLysineMaleMethionineMutationHistonesLysineMethionine

Identifiers

PMID25200322
PMCPMC4201755

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Registered trials

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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.