Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas
Abstract
Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin. About 50% of patients with STS experience relapse and more than 30% will die within 10 years after diagnosis. In this study we investigated circulating free DNA (cfDNA) and tumor-specific genetic alterations therein (circulating tumor DNA, ctDNA) as diagnostic biomarkers. Plasma concentrations and fragmentation of cfDNA was analyzed with quantitative PCR. Patients with STS (n = 64) had significantly higher plasma concentrations and increased fragmentation of cfDNA when compared to patients in complete remission (n = 19) and healthy controls (n = 41) (p < 0.01 and p < 0.001). Due to overlapping values between patients with STS and controls, the sensitivity and specificity of these assays is limited. Sensitive assays to detect genomic alterations in cfDNA of synovial sarcomas (t(X;18)), myxoid liposarcomas (t(12;16) and TERT C228T promoter mutation) and well-differentiated/de-differentiated liposarcomas (MDM2 amplifications) were established. ctDNA was quantified in nine liposarcoma patients during the course of their treatment. Levels of breakpoint t(12;16) and TERT C228T ctDNA correlated with the clinical course and tumor burden in patients with myxoid liposarcomas (n = 4). ctDNA could detect minimal residual disease and tumor recurrence. In contrast, detection of MDM2 amplifications was not sensitive enough to detect tumors in patients with well-differentiated/de-differentiated liposarcomas (n = 5). Genotyping of cfDNA for tumor specific genetic alterations is a feasible and promising approach for monitoring tumor activity in patients with myxoid liposarcomas. Detection of ctDNA during follow-up examinations despite negative standard imaging studies might warrant more sensitive imaging (e.g. PET-CT) or closer follow-up intervals to timely localize and treat recurrences.
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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 [24]
Tumor-informed ctDNA monitoring in osteosarcoma and breakpoint-guided ctDNA monitoring in translocation-associated sarcomas currently have the clearest longitudinal clinical support.
“Tumor-informed ctDNA monitoring in osteosarcoma and breakpoint-guided ctDNA monitoring in translocation-associated sarcomas currently have the clearest longitudinal clinical support, although both still require prospective multicenter validation before routine treatment decisions can be based on ctDNA alone [ 13 , 16 , 17 , 22 , 23 , 24 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [24]
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 [24]
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- Authors
- Braig, D., Becherer, C., Bickert, C., Braig, M., Claus, R., Eisenhardt, A. E., Heinz, J., Scholber, J., Herget, G. W., Bronsert, P., Fricke, A., Follo, M., Stark, G. B., Bannasch, H., & Eisenhardt, S. U.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Braig, David
- ORCID
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2019-03-09
- Volume
- 145
- Issue
- 4
- Pages
- 1148-1161
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2917570556
- Cited by
- 42
- References
- 30
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 3 · 2023: 2 · 2022: 9 · 2021: 10 · 2020: 4 · 2019: 2
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (396168587, EI 866/7‐1, CL 427/4‐1 and BR 5712/1‐1)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- cell-free DNA, circulating tumor DNA, myxoid liposarcoma, soft tissue sarcoma, non-invasive cancer detection, minimal residual disease, tumor recurrence monitoring, MDM2 amplification, synovial sarcoma, cfDNA fragmentation, diagnostic biomarkers
- MeSH terms
- Positron Emission Tomography Computed Tomography, Cell-Free Nucleic Acids, Circulating Tumor DNA, Female, Genotype, Humans, Male, Mutation, Neoplasm Recurrence, Local, Soft Tissue Neoplasms, Biomarkers, Tumor, Case-Control Studies, Liposarcoma, Myxoid, Cell Line, Tumor
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