IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours
Open accessAbstract
Somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in gliomas and acute myeloid leukaemia (AML). Since patients with multiple enchondromas have occasionally been reported to have these conditions, we hypothesized that the same mutations would occur in cartilaginous neoplasms. Approximately 1200 mesenchymal tumours, including 220 cartilaginous tumours, 222 osteosarcomas and another ∼750 bone and soft tissue tumours, were screened for IDH1 R132 mutations, using Sequenom® mass spectrometry. Cartilaginous tumours and chondroblastic osteosarcomas, wild‐type for IDH1 R132, were analysed for IDH2 (R172, R140) mutations. Validation was performed by capillary sequencing and restriction enzyme digestion. Heterozygous somatic IDH1/IDH2 mutations, which result in the production of a potential oncometabolite, 2‐hydroxyglutarate, were only detected in central and periosteal cartilaginous tumours, and were found in at least 56% of these, ∼40% of which were represented by R132C. IDH1 R132H mutations were confirmed by immunoreactivity for this mutant allele. The ratio of IDH1:IDH2 mutation was 10.6 : 1. No IDH2 R140 mutations were detected. Mutations were detected in enchondromas through to conventional central and dedifferentiated chondrosarcomas, in patients with both solitary and multiple neoplasms. No germline mutations were detected. No mutations were detected in peripheral chondrosarcomas and osteochondromas. In conclusion, IDH1 and IDH2 mutations represent the first common genetic abnormalities to be identified in conventional central and periosteal cartilaginous tumours. As in gliomas and AML, the mutations appear to occur early in tumourigenesis. We speculate that a mosaic pattern of IDH‐mutation‐bearing cells explains the reports of diverse tumours (gliomas, AML, multiple cartilaginous neoplasms, haemangiomas) occurring in the same patient. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Various tumors, including glioma, secondary glioblastoma, and acute myeloid leukemia, harboring heterozygous point mutations in the active sites of IDH1/2 show dramatic increases in R-2-HG levels.
“Thus, various tumors, including glioma, secondary glioblastoma, and acute myeloid leukemia (AML), harboring heterozygous point mutations in the active sites of IDH1/2 show dramatic increases in the R-2-HG levels111,113–115.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [114]
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- Authors
- Amary, M. F., Bacsi, K., Maggiani, F., Damato, S., Halai, D., Berisha, F., Pollock, R., O'Donnell, P., Grigoriadis, A., Diss, T., Eskandarpour, M., Presneau, N., Hogendoorn, P. C., Futreal, A., Tirabosco, R., & Flanagan, A. M.
- Affiliations
- Royal National Orthopaedic Hospital NHS Trust (GB)
- Guy's Hospital (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- University College London (GB)
- Leiden University (NL)
- Royal National Orthopaedic Hospital (GB)
- ORCID
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2011-05-19
- Volume
- 224
- Issue
- 3
- Pages
- 334-343
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2011376261
- Cited by
- 1,023
- References
- 53
- Citations by year
- 2026: 52 · 2025: 51 · 2024: 56 · 2023: 49 · 2022: 71 · 2021: 87 · 2020: 82 · 2019: 64 · 2018: 82 · 2017: 78 · 2016: 60 · 2015: 75 · 2014: 72 · 2013: 60 · 2012: 56
- FWCI
- 49.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Skeletal Cancer Action Trust (SCAT) UK
- Topics
- Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- IDH1 mutation, IDH2 mutation, central chondrosarcoma, periosteal chondroma, enchondroma, cartilaginous tumors, 2-hydroxyglutarate, somatic mutations, tumourigenesis, IDH1 R132H mutation, osteochondroma
- MeSH terms
- Bone Neoplasms, Chondroma, Chondrosarcoma, Enchondromatosis, Female, Follow-Up Studies, Humans, Isocitrate Dehydrogenase, Magnetic Resonance Imaging, Male, Mutation, Osteosarcoma, Germ-Line Mutation
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