Improved Quantification of Circulating Tumor DNA in Translocation‐Associated Myxoid Liposarcoma by Simultaneous Detection of Breakpoints and Single Nucleotide Variants
Open accessAbstract
Background: Myxoid liposarcomas (MLS) can exhibit a disseminated metastatic pattern, necessitating extensive diagnostics during follow‐up. With no tumor markers available, early diagnosis of recurrences and tumor monitoring is difficult. The detection of circulating tumor DNA (ctDNA; liquid biopsy) in MLS with the characteristic translocations t(12;16) and t(12;22) can provide an additional diagnostic. However, due to the often very low tumor fraction, distinguishing actual tumor variants from sequencing artifacts remains a key challenge. Methods: Using MLS as a model for translocation‐driven tumors, this study evaluates a refined analytical approach for detecting both single nucleotide variants (SNVs) and structural variants (SVs) with the highest possible sensitivity and specificity. Different analysis pipelines using Unique Molecular Identifiers (UMIs) were compared in dilution series of tumor DNA from MLS patients (n = 11) and a cell line. The results were validated on plasma samples (n = 36) from two MLS patients and one patient with Synovial Sarcoma (SS). Results: In dilution series, the use of UMIs significantly reduced false positive events in SNV analysis while maintaining high sensitivity without significant differences. In SV analysis, the effect of UMIs was not consistently detectable, as some dilution series exhibited no false positive events even without UMI correction. Additional filter criteria further improved specificity without significantly compromising assay sensitivity. Validation on patient plasma samples confirmed these findings, demonstrating the advantages of the differentiated analytical approach. Conclusion: By integrating a refined analytical approach for SNVs and SVs, we achieved reliable ctDNA detection that corresponded with the clinical course of the patients’ disease. This method enables non‐invasive tumor detection in translocation‐driven tumors with low mutational burden and can easily be adapted into routine clinical diagnostics.
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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 [15]
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 [15]
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 [15]
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Alabid, I., Yousef, A. J., Patni, M. M., Aloti, R. A., Qassim, Z. A.-A. M., Alothman-Agha, A. A., Hamdy, H. A., Noury, F. M., & Abdelfattah, M. T. (2026) · Cells · doi:10.3390/cells15141271
- Authors
- Schmid, A., Lausch, U., Runkel, A., Kiefer, J., Pauli, T., Boerries, M., Bogner, B., Eisenhardt, S. U., & Braig, D.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Schmid, A.
- Venue
- Cancer Medicine
- Publisher
- Wiley
- Published
- 2025-02
- Volume
- 14
- Issue
- 4
- Pages
- e70704-e70704
- ISSN
- 2045-7634 (ISSN-L)
- PMC
- PMC11842865
- OpenAlex
- W4407824582
- Cited by
- 4
- References
- 30
- Citations by year
- 2026: 3 · 2025: 1
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (396168587, BR 5712/1‐3, EI 866/7‐3)
- 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 › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- myxoid liposarcoma, circulating tumor DNA, liquid biopsy, single nucleotide variants, structural variants, unique molecular identifiers, tumor fraction, false positive reduction, synovial sarcoma, cancer monitoring, low mutational burden
- MeSH terms
- Liquid Biopsy, Circulating Tumor DNA, Adult, Aged, Female, Humans, Male, Middle Aged, Translocation, Genetic, Biomarkers, Tumor, Liposarcoma, Myxoid, Polymorphism, Single Nucleotide, Cell Line, Tumor, Chromosome Breakpoints, High-Throughput Nucleotide Sequencing
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