Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas
Open accessAbstract
Background: Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection. Methods: We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses SS18 (SYT) in chromosome 18 to SSX1 or SSX2 in chromosome x, and recurrent point mutations. In addition, patient-specific panels were designed from tumor exome sequencing. Both approaches were used to quantify ctDNA in patients’ plasma. Results: The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples (n = 11) from one patient collected over 3 years, with a patient-specific panel based on tumor exome sequencing, correlated with the clinical course, response to treatment and tumor volume. Conclusions: Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics.
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In synovial sarcoma and myxoid liposarcoma, subtype-matched structural-variant tracking supports aligning assay design with tumor biology.
“In synovial sarcoma and myxoid liposarcoma, subtype-matched structural-variant tracking further supports the need to align assay design with tumor biology [ 14 , 15 , 24 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [14]
Fusion-driven tumors may be best suited to breakpoint-guided ddPCR or fusion-aware NGS.
“Fusion-driven tumors may be best suited to breakpoint-guided ddPCR or fusion-aware NGS [ 13 , 14 , 15 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [14]
Synovial sarcoma and myxoid liposarcoma illustrate the value of structural-variant or breakpoint-informed approaches.
“Synovial sarcoma and myxoid liposarcoma similarly illustrate the value of structural-variant or breakpoint-informed approaches, although available cohorts remain limited and assay standardization is still needed [ 14 , 15 , 24 , 35 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [14]
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- Authors
- Eisenhardt, A. E., Brugger, Z., Lausch, U., Kiefer, J., Zeller, J., Runkel, A., Schmid, A., Bronsert, P., Wehrle, J., Leithner, A., Liegl-Atzwanger, B., Giunta, R. E., Eisenhardt, S. U., & Braig, D.
- Affiliations
- University of Freiburg (DE)
- Medical University of Graz (AT)
- Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
- LMU Klinikum (DE)
- Corresponding author
- Braig, David
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2022-04-21
- Volume
- 14
- Issue
- 9
- Pages
- 2078
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC9105697
- OpenAlex
- W4224250160
- Cited by
- 18
- References
- 34
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 1
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- 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
- synovial sarcoma, circulating tumor DNA, liquid biopsy, targeted next-generation sequencing, tumor recurrence monitoring, tumor volume, variant allele frequency, somatic mutations
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