ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mutant IDH is sufficient to initiate enchondromatosis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 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.
What it found
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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.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Prognostic importance of IDH mutations in chondrosarcoma: An individual patient data meta-analysis.Cancer medicine · 2021Pooled it
- Precision oncology in the treatment of patients with bone sarcomas: an up-to-date narrative review.Exploration of targeted anti-tumor therapy · 2026Review
- Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma.Genome biology · 2025Article
- Dnmt1 determines bone length by regulating energy metabolism of growth plate chondrocytes.Nature communications · 2025Article
- Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Long-term Safety and Clinical Activity in Patients with Conventional Chondrosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.The Journal of biological chemistry · 2025Article
- Protein Phosphatase 1 Regulatory Subunit 3C integrates cholesterol metabolism and isocitrate dehydrogenase in chondrocytes and neoplasia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.Acta biochimica et biophysica Sinica · 2025Review
- Chondrosarcoma: New Molecular Insights, Challenges in Near-Patient Preclinical Modeling, and Therapeutic Approaches.International journal of molecular sciences · 2025Review
- IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.Targeted oncology · 2025Review
- Single cell analysis of Idh mutant growth plates identifies cell populations responsible for longitudinal bone growth and enchondroma formation.Scientific reports · 2024Article
- IDH inhibition in gliomas: from preclinical models to clinical trials.Nature reviews. Neurology · 2024Review
- Single-cell transcriptomic analyses of mouse idh1 mutant growth plate chondrocytes reveal distinct cell populations responsible for longitudinal growth and enchondroma formation.Research square · 2024Article
- Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms.Nature communications · 2024Article
- A single-cell atlas of conventional central chondrosarcoma reveals the role of endoplasmic reticulum stress in malignant transformation.Communications biology · 2024Article
- Active site remodeling in tumor-relevant IDH1 mutants drives distinct kinetic features and potential resistance mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Hedgehog activation promotes osteogenic fates of growth plate resting zone chondrocytes through transient clonal competency.JCI insight · 2024Article
- Are IDH1 R132 Mutations Associated With Poor Prognosis in Patients With Chondrosarcoma of the Bone?Clinical orthopaedics and related research · 2024Article
- IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.BMC cancer · 2023Article
- Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
Enchondromas are benign cartilage tumors and precursors to malignant chondrosarcomas. Somatic mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2) are present in the majority of these tumor types. How these mutations cause enchondromas is unclear. Here, we identified the spectrum of IDH mutations in human enchondromas and chondrosarcomas and studied their effects in mice. A broad range of mutations was identified, including the previously unreported IDH1-R132Q mutation. These mutations harbored enzymatic activity to catalyze α-ketoglutarate to d-2-hydroxyglutarate (d-2HG). Mice expressing Idh1-R132Q in one allele in cells expressing type 2 collagen showed a disordered growth plate, with persistence of type X-expressing chondrocytes. Chondrocyte cell cultures from these animals or controls showed that there was an increase in proliferation and expression of genes characteristic of hypertrophic chondrocytes with expression of Idh1-R132Q or 2HG treatment. Col2a1-Cre;Idh1-R132Q mutant knock-in mice (mutant allele expressed in chondrocytes) did not survive after the neonatal stage. Col2a1-Cre/ERT2;Idh1-R132 mutant conditional knock-in mice, in which Cre was induced by tamoxifen after weaning, developed multiple enchondroma-like lesions. Taken together, these data show that mutant IDH or d-2HG causes persistence of chondrocytes, giving rise to rests of growth-plate cells that persist in the bone as enchondromas.
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Registered trials
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.