ArticleOncotarget2019
Characterization of cancer-associated IDH2 mutations that differ in tumorigenicity, chemosensitivity and 2-hydroxyglutarate production.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- State of the Art of IDH Inhibitors: Emerging Questions and Perspectives.Anti-cancer agents in medicinal chemistry · 2026Review
- Blast Clearance Dynamics and Time to Response AcrossEJHaem · 2025Article
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma.Biomedicines · 2024Article
- Proteomic Profiling Identifies Predictive Signatures for Progression Risk in Patients with Advanced-Stage Follicular Lymphoma.Cancers · 2024Article
- IDH2/R140Q mutation confers cytokine-independent proliferation of TF-1 cells by activating constitutive STAT3/5 phosphorylation.Cell communication and signaling : CCS · 2024Article
- Fusarium oxysporum f. sp.mBio · 2023Article
- Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis.International journal of molecular sciences · 2023Review
- Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia.Cancers · 2021Article
- Biological Roles and Therapeutic Applications of IDH2 Mutations in Human Cancer.Frontiers in oncology · 2021Review
- (2Cancers · 2020Article
- Identification of High-Order Single-Nucleotide Polymorphism Barcodes in Breast Cancer Using a Hybrid Taguchi-Genetic Algorithm: Case-Control Study.JMIR medical informatics · 2020Article
- The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis.Cancers · 2020Article
- Targeting epigenetic regulators in the treatment of T-cell lymphoma.Expert review of hematology · 2020Review
- Pharmacological characterization of TQ05310, a potent inhibitor of isocitrate dehydrogenase 2 R140Q and R172K mutants.Cancer science · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The family of isocitrate dehydrogenase (IDH) enzymes is vital for cellular metabolism, as IDH1 and IDH2 are required for the decarboxylation of isocitrate to α-ketoglutarate. Heterozygous somatic mutations in IDH1 or IDH2 genes have been detected in many cancers. They share the neomorphic production of the oncometabolite (R)-2-hydroxyglutarate [(R)-2-HG]. With respect to IDH2, it is unclear whether all IDH2 mutations display the same or differ in tumorigenic properties and degrees of chemosensitivity. Here, we evaluated the three most frequent IDH2 mutations occurring in cancer. The predicted changes to the enzyme structure introduced by these individual mutations are supported by the observed production of (R)-2-HG. However, their tumorigenic properties, response to chemotherapeutic agents, and baseline activation of STAT3 differed. Paradoxically, the varying levels of endogenous (R)-2-HG produced by each IDH2 mutant inversely correlated with their respective growth rates. Interestingly, while we found that (R)-2-HG stimulated the growth of non-transformed cells, (R)-2-HG also displayed antitumor activity by suppressing the growth of tumors harboring wild type IDH2. The mitogenic effect of (R)-2-HG in immortalized cells could be switched to antiproliferative by transformation with oncogenic RAS. Thus, our findings show that despite their shared (R)-2-HG production, IDH2 mutations are not alike and differ in shaping tumor cell behavior and response to chemotherapeutic agents. Our study also reveals that under certain conditions, (R)-2-HG has antitumor properties.
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