Cancer-associated IDH mutations: biomarker and therapeutic opportunities

Yen, K E; Bittinger, M A; Su, S M; Fantin, V R

doi:10.1038/onc.2010.444

Cited by 296Glioma Diagnosis and TreatmentCancer, Hypoxia, and MetabolismAcute Myeloid Leukemia Research

Cancer-associated IDH mutations: biomarker and therapeutic opportunities

Yen, K E, Bittinger, M A, Su, S M, Fantin, V R·2010·Oncogene

DOI 10.1038/onc.2010.444

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Abstract

The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology. The nature of the heterozygous, point mutations mapping to arginine residues involved in the substrate binding inspired several research teams to investigate their impact on the biochemical activity of these enzymes. Soon, it became clear that the mutations identified impaired the ability of IDH1 and IDH2 to catalyze the conversion of isocitrate to α-ketoglutarate (αKG), whereas conferring a gain of a novel enzymatic activity leading to the reduction of αKG to the metabolite D2-hydroxyglutarate (D-2HG). Across glioma as well as several hematologic malignancies, mutations in IDH1 and IDH2 have shown prognostic value. Several hypotheses implicating the elevated levels of D-2HG and tumorigenesis, and the therapeutic potential of targeting mutant IDH enzymes will be discussed.

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IDH1 or IDH2 mutations produce the oncometabolite D-2-hydroxyglutarate.
“IDH1 or IDH2 mutations lead to production of the oncometabolite D2-hydroxyglutarate (D-2HG) (Yen et al., 2010).”
From SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways (2013) · cites this paper as Yen et al., 2010

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Self-citation

Authors: Yen, K. E., Bittinger, M. A., Su, S. M., & Fantin, V. R.
Affiliations: Agios Pharmaceuticals (United States) (US)
Corresponding author: Fantin, V R
ORCID: Yen, K E
Fantin, V R
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2010-10-25
Volume: 29
Issue: 49
Pages: 6409-6417
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/onc.2010.444
OpenAlex: W2002134084
Cited by: 296
References: 63
Citations by year: 2026: 3 · 2025: 8 · 2024: 11 · 2023: 17 · 2022: 16 · 2021: 23 · 2020: 21 · 2019: 21 · 2018: 22 · 2017: 23 · 2016: 16 · 2015: 16 · 2014: 18 · 2013: 29 · 2012: 27
FWCI: 2.93
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords: IDH mutation, IDH1, IDH2, glioblastoma, glioma, hematologic malignancies, gain-of-function mutations, alpha-ketoglutarate, prognostic factors, carcinogenesis
MeSH terms: Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Oncogenes, Biomarkers, Tumor, Central Nervous System Neoplasms, Point Mutation, Hematologic Neoplasms

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