Digital PCR analysis of circulating tumor DNA: A biomarker for chondrosarcoma diagnosis, prognostication, and residual disease detection
Open accessAbstract
Conventional chondrosarcoma is the most common primary bone tumor in adults. Prognosis corresponds with tumor grade but remains variable, especially for individuals with grade (G) II disease. There are currently no biomarkers available for monitoring or prognostication of chondrosarcoma. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for a broad range of tumor types. To date, little has been done to study the presence of ctDNA and its potential utility in the management of sarcomas, including chondrosarcoma. In this study, we have assessed ctDNA levels in a cohort of 71 patients, 32 with sarcoma, including 29 individuals with central chondrosarcoma (CS) and 39 with locally aggressive and benign bone and soft tissue tumors, using digital PCR. In patients with CS, ctDNA was detected in pretreatment samples in 14/29 patients, which showed clear correlation with tumor grade as demonstrated by the detection of ctDNA in all patients with GIII and dedifferentiated disease (n = 6) and in 8/17 patients with GII disease, but never associated with GI CS. Notably detection of ctDNA preoperatively in GII disease was associated with a poor outcome. A total of 14 patients with CS had ctDNA levels assessed at multiple time points and in most patients there was a clear reduction following surgical removal. This research lays the foundation for larger studies to assess the utility of ctDNA for chondrosarcoma diagnosis, prognostication, early detection of residual disease and monitoring disease progression.
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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 [20]
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 [20]
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 [20]
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 [20]
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 [20]
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References 30 · Cited by 38
Research works printed but not linked: 1
- [1]Evans, H. L., A. G. Ayala, and M. M. Romsdahl. 1977 Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer 40: 818– 831. 890662
- Authors
- Gutteridge, A., Rathbone, V. M., Gibbons, R., Bi, M., Archard, N., Davies, K. E. J., Brown, J., Plagnol, V., Pillay, N., Amary, F., O'Donnell, P., Gupta, M., Tirabosco, R., Flanagan, A. M., & Forshew, T.
- Affiliations
- University College London (GB)
- Royal National Orthopaedic Hospital NHS Trust (GB)
- Howard Hughes Medical Institute (US)
- Royal National Orthopaedic Hospital NHS Trust (Radiology) Stanmore United Kingdom
- Corresponding author
- Flanagan, Adrienne M.
- ORCID
- Venue
- Cancer Medicine
- Publisher
- Wiley
- Published
- 2017-08-23
- Volume
- 6
- Issue
- 10
- Pages
- 2194-2202
- ISSN
- 2045-7634 (ISSN-L)
- PMC
- PMC5633548
- OpenAlex
- W2745690890
- Cited by
- 38
- References
- 30
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 4 · 2019: 3 · 2018: 4
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Sarcoma UK
- National Institute for Health Research
- 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
- chondrosarcoma, circulating tumor DNA, liquid biopsy, digital PCR, tumor grade, prognostic factors, residual disease detection, dedifferentiated chondrosarcoma, bone tumors, soft tissue tumor, disease surveillance
- MeSH terms
- Circulating Tumor DNA, Bone Neoplasms, Chondrosarcoma, Humans, Isocitrate Dehydrogenase, Mutation, Prognosis, Biomarkers, Tumor, Polymerase Chain Reaction, Neoplasm, Residual, Kaplan-Meier Estimate
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