Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations
Open accessAbstract
Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.
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Methylation-based approaches may provide value in osteosarcoma, chordoma, and other low-mutation contexts.
“while methylation-based approaches may provide value in osteosarcoma, chordoma, and other low-mutation contexts [ 18 , 19 , 20 , 21 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [18]
Mutation-based assays may be informative in selected chondrosarcoma cases.
“Similarly, mutation-based assays may be informative in selected chondrosarcoma cases”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [18]
Mutation-defined subtypes may be suited to hotspot assays when the mutation is stable and tumor-specific.
“Mutation-defined subtypes may be suited to hotspot assays when the mutation is stable and tumor-specific [ 18 , 20 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [18]
In chondrosarcoma and chordoma, mutation- and methylation-based strategies may be informative in selected molecularly defined cases.
“In chondrosarcoma and chordoma, mutation- and methylation-based strategies may be informative in selected molecularly defined cases, but these approaches are not universally applicable across all patients [ 18 , 19 , 20 , 38 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [18]
Mutation- and methylation-based strategies are not universally applicable across all chondrosarcoma and chordoma patients.
“In chondrosarcoma and chordoma, mutation- and methylation-based strategies may be informative in selected molecularly defined cases, but these approaches are not universally applicable across all patients [ 18 , 19 , 20 , 38 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [18]
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- Authors
- Lyskjær, I., Davies, C., Strobl, A., Hindley, J., James, S., Lalam, R. K., Cross, W., Hide, G., Rankin, K. S., Jeys, L., Tirabosco, R., Stevenson, J., Genomics England Research Consortium, O’Donnell, P., Cool, P., & Flanagan, A. M.
- Affiliations
- University College London (GB)
- Royal National Orthopaedic Hospital (GB)
- Royal Orthopaedic Hospital (GB)
- Freeman Hospital (GB)
- Robert Jones and Agnes Hunt Orthopaedic Hospital (GB)
- Corresponding author
- Flanagan, Adrienne M.
- ORCID
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2021-09-30
- Volume
- 15
- Issue
- 12
- Pages
- 3679-3690
- ISSN
- 1574-7891 (ISSN-L)
- 1878-0261
- PMC
- PMC8637565
- OpenAlex
- W3200307827
- Cited by
- 16
- References
- 32
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2023: 2 · 2022: 2
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- WestminsterResearch (University of Westminster) (acceptedVersion, cc-by)
- Keele Research Repository (Keele University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- UCLH Biomedical Research Centre
- Lundbeckfonden (R303‐2018‐3018)
- National Institute for Health Research
- Bone Cancer Research Trust
- Sarcoma UK (SUKG01.2018)
- 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 › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- central chondrosarcoma, circulating tumor DNA, liquid biopsy, IDH1 mutation, IDH2 mutation, GNAS mutation, risk stratification, prognosis, tumor grade, bone tumors, blood-based biomarkers
- MeSH terms
- Circulating Tumor DNA, Adult, Chondrosarcoma, Chromogranins, Humans, Isocitrate Dehydrogenase, Mutation, Biomarkers, Tumor, Risk Assessment, GTP-Binding Protein alpha Subunits, Gs
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