Central atypical cartilaginous tumour / chondrosarcoma, grade 1
Primary Author(s)*
Kathleen Schieffer, PhD, FACMG
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Soft Tissue and Bone Tumours (5th ed.) |
| Category | Bone tumours |
| Family | Chondrogenic tumours |
| Type | Central atypical cartilaginous tumour / chondrosarcoma, grade 1 |
| Subtype(s) | N/A |
Related Terminology
| Acceptable | Low-grade central chondrosarcoma |
| Not Recommended | N/A |
Gene Rearrangements
None
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Individual Region Genomic Gain/Loss/LOH
None
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Characteristic Chromosomal or Other Global Mutational Patterns
None
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
| N/A | N/A | N/A | N/A | N/A | N/A |
Gene Mutations (SNV/INDEL)
Hotspot alterations in IDH1 and IDH2 are commonly observed in central atypical cartilaginous tumour / chondrosarcoma, grade 1.
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| IDH1 and IDH2 | Hotspot alterations at IDH1 p.Arg132 or IDH2 p.Arg172;
rarely IDH1 p.Arg140 |
Oncogene | Common | D, T | Yes (WHO, NCCN) | Nearly half (50%) of central atypical cartilaginous tumour / chondrosarcoma, grade 1 harbor hotspot alterations in IDH1 (p.Arg132) or IDH2 (p.Arg172)[1][2][3][4][5][6] or rarely in IDH1 p.Arg140)[7]. In the setting of central atypical cartilaginous tumour / chondrosarcoma, grade 1 occurring in the setting of enchondromatosis (i.e. Ollier disease and Maffucci syndrome), IDH1 or IDH2 alterations are found in nearly 78% of cases[1][2][3]. The use of IDH inhibitors is understudy for use in conventional chondrosarcomas harboring an IDH1 or IDH2 alteration[8]. Comprehensive genomic testing across various histological subgroups of chondrosarcoma are ongoing[6]. |
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
None
Genes and Main Pathways Involved
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| IDH1 and IDH2 | Histone modification | Hotspot alterations in IDH1 and IDH2 have been shown to reduce oxidative carboxylation of isocitrate and instead, catalyze the NADPH-dependent reduction of alpha-ketoglutarate to 2-hydroxyglutarate which alters specific histone markers and induces DNA hypermethylation[9]. |
Genetic Diagnostic Testing Methods
- Targeted sequencing
- Targeted sequencing of IDH1 and/or IDH2 hotspots would identify the genomic driver in at least half of cases.
Familial Forms
Central atypical cartilaginous tumour / chondrosarcoma, grade 1 may occur in the setting of enchondromatosis (i.e. Ollier disease and Maffucci syndrome).
Additional Information
None
Links
None
References
- ↑ 1.0 1.1 Amary, M. Fernanda; et al. (2011-07). "IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours". The Journal of Pathology. 224 (3): 334–343. doi:10.1002/path.2913. ISSN 1096-9896. PMID 21598255. Check date values in:
|date=(help) - ↑ 2.0 2.1 Pansuriya, Twinkal C.; et al. (2011-11-06). "Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome". Nature Genetics. 43 (12): 1256–1261. doi:10.1038/ng.1004. ISSN 1546-1718. PMC 3427908. PMID 22057234.
- ↑ 3.0 3.1 Amary, M. Fernanda; et al. (2011-11-06). "Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2". Nature Genetics. 43 (12): 1262–1265. doi:10.1038/ng.994. ISSN 1546-1718. PMID 22057236.
- ↑ Scotlandi, Katia; et al. (2020-04-14). "Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors". Cells. 9 (4): 968. doi:10.3390/cells9040968. ISSN 2073-4409. PMC 7227002 Check
|pmc=value (help). PMID 32295254 Check|pmid=value (help). - ↑ Lyskjaer, Iben; et al. (2021-12). "Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations". Molecular Oncology. 15 (12): 3679–3690. doi:10.1002/1878-0261.13102. ISSN 1878-0261. PMC 8637565 Check
|pmc=value (help). PMID 34528398 Check|pmid=value (help). Check date values in:|date=(help) - ↑ 6.0 6.1 Meijer, Debora M.; et al. (2025-09-19). "An Integrated Clinical Genomic and Transcriptomic Subgrouping of Central Chondrosarcoma". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 38 (12): 100894. doi:10.1016/j.modpat.2025.100894. ISSN 1530-0285. PMID 40976495 Check
|pmid=value (help). - ↑ Lugowska, Iwona; et al. (2018). "IDH1/2 Mutations Predict Shorter Survival in Chondrosarcoma". Journal of Cancer. 9 (6): 998–1005. doi:10.7150/jca.22915. ISSN 1837-9664. PMC 5868167. PMID 29581779.
- ↑ Tap, William D.; et al. (2025-06-03). "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. 31 (11): 2108–2114. doi:10.1158/1078-0432.CCR-24-4128. ISSN 1557-3265. PMC 12130799 Check
|pmc=value (help). PMID 40100120 Check|pmid=value (help). - ↑ Turcan, Sevin; et al. (2012-02-15). "IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype". Nature. 483 (7390): 479–483. doi:10.1038/nature10866. ISSN 1476-4687. PMC 3351699. PMID 22343889.
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Prior Author(s): *Citation of this Page: “Central atypical cartilaginous tumour / chondrosarcoma, grade 1”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/14/2025, https://ccga.io/index.php/STBT5:Central atypical cartilaginous tumour / chondrosarcoma, grade 1.