ArticleCancer & metabolism2021
Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes.
Article in Cancer & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- The Role of AXL Signaling and MutantCancers · 2026Review
- Review
- Advances in the Molecular Biology of Chondrosarcoma for Drug Discovery and Precision Medicine.Cancers · 2025Review
- 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
- 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
- (B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.Cell death and differentiation · 2025Review
- Neomorphic IDH Heterodimer Mutants: An Underestimated Point in Cancer Pathogenesis.Current cancer drug targets · 2025Review
- Article
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- Hunting for the vulnerability in chondrosarcoma by tracing metabolic and genetic links.Cell reports. Medicine · 2024Article
- Expression and Prognostic Role of PANK1 in Glioma.Combinatorial chemistry & high throughput screening · 2024Article
- Metabolic Profiles Point Out Metabolic Pathways Pivotal in Two Glioblastoma (GBM) Cell Lines, U251 and U-87MG.Biomedicines · 2023Article
- Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation.Cell reports · 2023Article
- A Case Report and Brief Literature Review on Dedifferentiated Chondrosarcoma in Proximal Phalanx: A Rare Location.Cureus · 2022Article
- Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Metabolic Pathways and Targets in Chondrosarcoma.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMajority of chondrosarcomas are associated with a number of genetic alterations, including somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, but the downstream effects of these mutated enzymes on cellular metabolism and tumor energetics are unknown. As IDH mutations are likely to be involved in malignant transformation of chondrosarcomas, we aimed to exploit metabolomic changes in IDH mutant and non-mutant chondrosarcomas.
methodsHere, we profiled over 69 metabolites in 17 patient-derived xenografts by targeted mass spectrometry to determine if metabolomic differences exist in mutant IDH1, mutant IDH2, and non-mutant chondrosarcomas. UMAP (Uniform Manifold Approximation and Projection) analysis was performed on our dataset to examine potential similarities that may exist between each chondrosarcoma based on genotype.
resultsUMAP revealed that mutant IDH chondrosarcomas possess a distinct metabolic profile compared with non-mutant chondrosarcomas. More specifically, our targeted metabolomics study revealed large-scale differences in organic acid intermediates of the tricarboxylic acid (TCA) cycle, amino acids, and specific acylcarnitines in chondrosarcomas. Lactate and late TCA cycle intermediates were elevated in mutant IDH chondrosarcomas, suggestive of increased glycolytic metabolism and possible anaplerotic influx to the TCA cycle. A broad elevation of amino acids was found in mutant IDH chondrosarcomas. A few acylcarnitines of varying carbon chain lengths were also elevated in mutant IDH chondrosarcomas, but with minimal clustering in accordance with tumor genotype. Analysis of previously published gene expression profiling revealed increased expression of several metabolism genes in mutant IDH chondrosarcomas, which also correlated to patient survival.
conclusionsOverall, our findings suggest that IDH mutations induce global metabolic changes in chondrosarcomas and shed light on deranged metabolic pathways.
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