Evidence map›Paper›PMID 27664011›Full record

ArticleActa neuropathologica2016

Mutant IDH1 and thrombosis in gliomas.

Dusten Unruh, Steven R Schwarze, Laith Khoury, Cheddhi Thomas, Meijing Wu, Li Chen, Rui Chen, Yinxing Liu, Margaret A Schwartz, Christina Amidei and 14 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 3 pooled it
9.1field-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.

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

98 citing papers in PubMed, 3 syntheses or guidelines pooled it, 171 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Review
  5. Article
  6. Article
  7. Tumor treating fields alter local coagulation dynamics in glioblastoma patients.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  8. Article
  9. Review
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  11. Review
  12. Article
  13. Cancers · 2025
    Article
  14. A clinically relevant model and method to study necrosis as a driving force in glioma restructuring and progression.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  15. Review
  16. Article
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38 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

24 authors at 4 institutions in 2 countries.

Dusten UnruhDepartment of Neurosurgery, Northwestern University, Tarry 2-705, 300 East Superior Street, Chicago, IL, 60611, USA.
Steven R SchwarzeDepartment of Pathology, University of Kentucky, Lexington, KY, USA.
Laith KhouryDepartment of Neurosurgery, University of Kentucky, Lexington, KY, USA.
Cheddhi ThomasDepartment of Pathology, New York University, New York, NY, USA.
Meijing WuDepartment of Neurosurgery, Northwestern University, Tarry 2-705, 300 East Superior Street, Chicago, IL, 60611, USA.
Li ChenDepartment of Biostatistics, University of Kentucky, Lexington, KY, USA.
Rui ChenDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA.
Yinxing LiuDepartment of Pathology, University of Kentucky, Lexington, KY, USA.
Margaret A SchwartzDepartment of Neurology, Northwestern University, Chicago, IL, USA.
Christina AmideiDepartment of Neurosurgery, Northwestern University, Tarry 2-705, 300 East Superior Street, Chicago, IL, 60611, USA.
Priya KumthekarDepartment of Neurology, Northwestern University, Chicago, IL, USA.
Carolina G BenjaminDepartment of Neurosurgery, New York University, New York, NY, USA.
Kristine SongUniversity of Kentucky, Lexington, KY, USA.
Caleb DawsonUniversity of Kentucky, Lexington, KY, USA.
Joanne M RispoliDepartment of Radiology, New York University, New York, NY, USA.
Girish FatterpekarDepartment of Radiology, New York University, New York, NY, USA.
John G GolfinosDepartment of Neurosurgery, New York University, New York, NY, USA.
Douglas KondziolkaDepartment of Neurosurgery, New York University, New York, NY, USA.
Matthias KarajannisDepartment of Pediatrics, New York University, New York, NY, USA.
Donato PacioneDepartment of Neurosurgery, New York University, New York, NY, USA.
David ZagzagDepartment of Pathology, New York University, New York, NY, USA.
Thomas McIntyreDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH, USA.
Matija SnuderlDepartment of Pathology, New York University, New York, NY, USA.
Craig HorbinskiDepartment of Neurosurgery, Northwestern University, Tarry 2-705, 300 East Superior Street, Chicago, IL, 60611, USA. craig.horbinski@northwestern.edu.ORCID 0000-0001-8340-9992
New York University · USNorthwestern University · USUniversity of Kentucky · USCleveland Clinic · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI KATHLEEN L. O'CONNOR · 2013 to 2026
$38.3M
SAMPLE COREU24DK097215 · NIDDK · UNIVERSITY OF KENTUCKY · PI FAN, TERESA WHEI-MEI, HIGASHI, RICHARD M · 2013 to 2017
$8.7M
The Significance of Isocitrate Dehydrogenase Mutations in GliomasK08CA155764 · NCI · UNIVERSITY OF KENTUCKY · PI HORBINSKI, CRAIG MICHAEL · 2011 to 2015
$857k
NCI NIH HHS K08 CA155764NCI NIH HHS P30 CA177558NIDDK NIH HHS U24 DK097215
6 · The paper itself

Abstract

Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

Indexed as

AdultAgedAged, 80 and overAlcohol OxidoreductasesAnimalsAntineoplastic AgentsBlood PlateletsBrain NeoplasmsCalcimycinCalcium IonophoresCohort StudiesFemaleGliomaHumansIsocitrate DehydrogenaseMaleAlcohol OxidoreductasesAntineoplastic AgentsCalcimycinCalcium IonophoresD-2-hydroxyacid dehydrogenaseIDH1 protein, humanIsocitrate DehydrogenaseThrombinThromboplastinD-2-hydroxyglutarateGliomaIsocitrate dehydrogenasePlateletThrombosisTissue factor

Identifiers

PMID27664011
PMCPMC5640980
OpenAlexW2523489572

What OpenQuestion holds

Textmetadata
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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.