Evidence map›Paper›PMID 40188944›Full record

ArticleThe Journal of biological chemistry2025

Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.

Ashley V Schwartz, Grace Chao, Mikella Robinson, Brittany M Conley, Mowaffaq Adam Ahmed Adam, Grace A Wells, An Hoang, Elene Albekioni, Cecilia Gallo, Joi Weeks and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Ashley V SchwartzComputational Science Research Center, San Diego State University, San Diego, California, USA.
Grace ChaoDepartment of Biology, San Diego State University, San Diego, California, USA.
Mikella RobinsonDepartment of Biology, San Diego State University, San Diego, California, USA.
Brittany M ConleyDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Mowaffaq Adam Ahmed AdamDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Grace A WellsDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
An HoangDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Elene AlbekioniDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Cecilia GalloDepartment of Biology, San Diego State University, San Diego, California, USA.
Joi WeeksDepartment of Biology, San Diego State University, San Diego, California, USA.
Katelyn YunkerDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Giovanni QuichochoDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Uduak Z GeorgeComputational Science Research Center, San Diego State University, San Diego, California, USA; Department of Mathematics and Statistics, San Diego State University, San Diego, California, USA.
Ingrid NiesmanElectron Microscope Facility, San Diego State University, San Diego, California, USA.
Carrie D HouseDepartment of Biology, San Diego State University, San Diego, California, USA.
Şevin TurcanNeurology Clinic and National Center for Tumor Diseases, Heidelberg University Hospital and Heidelberg University, Heidelberg, Germany. Electronic address: sevin.turcan@med.uni-heidelberg.de.
Christal D SohlDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA. Electronic address: csohl@sdsu.edu.

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
Research Education CoreU54CA132384 · NCI · SAN DIEGO STATE UNIVERSITY · PI CRIPPS, RICHARD MATTHEW, CROWE, SHEILA E. · 2008 to 2022
$20.7M
Research Education CoreU54CA132379 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ARREDONDO, ELVA M, CROWE, SHEILA E. · 2008 to 2021
$16.1M
THE INTERSECTION OF LANGUAGE AND AFFECTR25GM058906 · NIGMS · SAN DIEGO STATE UNIVERSITY · PI TONG, WILLIAM G. · 1999 to 2021
$10.7M
Isocitrate dehydrogenase (IDH) mutations as drivers of organelle stress and dysfunction"R35GM137773 · NIGMS · SAN DIEGO STATE UNIVERSITY · PI Christal Dyane Sohl · 2020 to 2026
$2.7M
Biophysical modeling of cis-regulatory complexes in transcription and splicing using massively parallel reporter assaysR35GM133777 · NIGMS · COLD SPRING HARBOR LABORATORY · PI KINNEY, JUSTIN B. · 2019 to 2023
$2.4M
Alternative NF-kB activation in post-chemotherapy setting to elucidate novel mechanisms of ovarian cancer relapseR01CA260281 · NCI · SAN DIEGO STATE UNIVERSITY · PI Carrie Danielle House · 2022 to 2026
$2.1M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA260281NCI NIH HHS U54 CA132379NCI NIH HHS U54 CA132384NIGMS NIH HHS R25 GM058906NIGMS NIH HHS R35 GM133777NIGMS NIH HHS R35 GM137773NIH HHS S10 OD026929
6 · The paper itself

Abstract

Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces D-2-hydroxyglutarate (D2HG), which can inhibit DNA demethylases to drive tumorigenesis. Mutations affect residue R132 and display distinct catalytic profiles for D2HG production. We show that catalytic efficiency of D2HG production is greater in IDH1 R132Q than R132H mutants, and expression of IDH1 R132Q in cellular and xenograft models leads to higher D2HG concentrations in cells, tumors, and sera compared to R132H. Though expression of IDH1 R132Q leads to hypermethylation in DNA damage pathways, DNA hypomethylation is more notable when compared to IDH1 R132H expression. Transcriptome analysis shows increased expression of many pro-tumor pathways upon expression of IDH1 R132Q versus R132H, including transcripts of EGFR and PI3K signaling pathways. Thus, IDH1 mutants appear to modulate D2HG levels via altered catalysis and are associated with distinct epigenetic and transcriptomic consequences, with higher D2HG levels appearing to be associated with more aggressive tumors.

Indexed as

Isocitrate DehydrogenaseMutationNeoplasmsAnimalsCell Line, TumorDNA MethylationGlutaratesHumansMicePhenotypealpha-hydroxyglutarateGlutaratesIDH1 protein, humanIsocitrate Dehydrogenasedehydrogenaseenzyme mutationepigeneticsoncogenetranscriptomics

Identifiers

PMID40188944
PMCPMC12147185

What OpenQuestion holds

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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.