Evidence map›Paper›PMID 25706986›Full record

ArticlePloS one2015

Metabolic reprogramming in mutant IDH1 glioma cells.

Jose L Izquierdo-Garcia, Pavithra Viswanath, Pia Eriksson, Myriam M Chaumeil, Russell O Pieper, Joanna J Phillips, Sabrina M Ronen

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

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  19. Metabolomics of Glioma.Advances in experimental medicine and biology · 2021
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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

7 authors at 3 institutions in 1 country.

Jose L Izquierdo-GarciaDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
Pavithra ViswanathDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
Pia ErikssonDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
Myriam M ChaumeilDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America.
Russell O PieperDepartment of Neurological Surgery, Helen Diller Research Center, University of California San Francisco, San Francisco, California, United States of America; Brain Tumor Research Center, University of California San Francisco, San Francisco, California, United States of America.
Joanna J PhillipsDepartment of Neurological Surgery, Helen Diller Research Center, University of California San Francisco, San Francisco, California, United States of America; Brain Tumor Research Center, University of California San Francisco, San Francisco, California, United States of America.
Sabrina M RonenDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America; Brain Tumor Research Center, University of California San Francisco, San Francisco, California, United States of America.
University of California System · USNeurological Surgery · USUniversity of California, San Francisco · US

Funding

Metabolic Reprogramming in Brain TumorsR01CA172845 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RONEN, SABRINA MIRIAM · 2013 to 2022
$6.3M
MR Metabolic Imaging of Response to Targeted Therapies in GBMR01CA154915 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NELSON, SARAH J., RONEN, SABRINA MIRIAM · 2011 to 2015
$2.7M
MR Imaging of IDH Mutational Status in Brain TumorsR21CA161545 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RONEN, SABRINA MIRIAM · 2012 to 2013
$360k
NCI NIH HHS R01 CA154915NCI NIH HHS R01CA154915NCI NIH HHS R01 CA172845NCI NIH HHS R01CA172845NCI NIH HHS R21 CA161545NCI NIH HHS R21CA161545
6 · The paper itself

Abstract

backgroundMutations in isocitrate dehydrogenase (IDH) 1 have been reported in over 70% of low-grade gliomas and secondary glioblastomas. IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate while mutant IDH1 catalyzes the conversion of α-ketoglutarate into 2-hydroxyglutarate. These mutations are associated with the accumulation of 2-hydroxyglutarate within the tumor and are believed to be one of the earliest events in the development of low-grade gliomas. The goal of this work was to determine whether the IDH1 mutation leads to additional magnetic resonance spectroscopy (MRS)-detectable changes in the cellular metabolome.

methodsTwo genetically engineered cell models were investigated, a U87-based model and an E6/E7/hTERT immortalized normal human astrocyte (NHA)-based model. For both models, wild-type IDH1 cells were generated by transduction with a lentiviral vector coding for the wild-type IDH1 gene while mutant IDH1 cells were generated by transduction with a lentiviral vector coding for the R132H IDH1 mutant gene. Metabolites were extracted from the cells using the dual-phase extraction method and analyzed by 1H-MRS. Principal Component Analysis was used to analyze the MRS data.

resultsPrincipal Component Analysis clearly discriminated between wild-type and mutant IDH1 cells. Analysis of the loading plots revealed significant metabolic changes associated with the IDH1 mutation. Specifically, a significant drop in the concentration of glutamate, lactate and phosphocholine as well as the expected elevation in 2-hydroxyglutarate were observed in mutant IDH1 cells when compared to their wild-type counterparts.

conclusionThe IDH1 mutation leads to several, potentially translatable MRS-detectable metabolic changes beyond the production of 2-hydroxyglutarate.

Indexed as

MutationBrain NeoplasmsGlioblastomaHumansIsocitrate DehydrogenaseIDH1 protein, humanIsocitrate Dehydrogenase

Identifiers

PMID25706986
PMCPMC4338038
OpenAlexW2058417905

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.