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Updated: Jan 3, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Prospective Evaluation of the Concordance of Commercial Circulating Tumor DNA Alterations with Tumor-Based Sequencing
Bryce Demoret1, Jeff Gregg2, David A Liebner1,3
1Division of Medical Oncology, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
Soft tissue sarcomas (STS) are diverse tumors with heterogenous alterations. Platforms to detect circulating tumor DNA (ctDNA) have rapidly increased in popularity as they may avoid invasive biopsy morbidity. However, ctDNA profiling concordance with standard solid tumor comprehensive genomic profiling (CGP) is poorly characterized. Here, we report the outcomes of a single-institution experience comparing mutational results from commercial ctDNA and solid tumor CGP in advanced STS subjects. We identified STS subjects who had undergone solid tumor based CGP in four distinct cohorts: Dedifferentiated liposarcoma (DDLPS), leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), and gastrointestinal stromal tumor (GIST). Subjects with radiographically measurable tumor were profiled using a commercial ctDNA CGP panel. Overlapping genes/exons on both biopsy panels were analyzed. Twenty-four subjects completed both ctDNA and solid tumor CGP. ctDNA was detected in 18/24 subjects. Subject level concordance rates in all overlapping genes were: LMS = 4/6; UPS = 2/6; DDLPS = 1/6; GIST = 0/6. Copy number alterations were notably poorly concordant. For subjects with short variant alterations and detectable tumor fractions, concordance with solid tumor CGP was 76% (13/17). LMS subjects had the highest median tumor fraction and concordance. No correlation was seen between tumor fraction or radiographic tumor volume largely driven by low estimated tumor fraction. A limitation of the study is that only targeted sequencing was performed. However, given the poor concordance in commonly altered genes, ctDNA panels in sarcoma cannot be broadly applied. Further, more extensive studies will need to be performed.
Insights
Liquid biopsy using circulating tumor DNA (ctDNA) shows low concordance with solid tumor genomic profiling in soft tissue sarcomas (STS). This suggests ctDNA panels are not yet broadly applicable for sarcoma mutation detection.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Soft tissue sarcomas (STS) are a heterogeneous group of tumors.
- Circulating tumor DNA (ctDNA) profiling offers a less invasive alternative to traditional biopsies.
- The concordance between ctDNA and solid tumor comprehensive genomic profiling (CGP) in STS is not well-established.
Purpose of the Study:
- To compare the mutational results from commercial ctDNA profiling with solid tumor CGP in advanced STS patients.
- To evaluate the concordance rates across different STS subtypes.
Main Methods:
- Retrospective analysis of 24 advanced STS patients who underwent both solid tumor CGP and ctDNA CGP.
- Analysis of overlapping genes and exons between the two profiling platforms.
- Comparison of concordance rates for short variant alterations and copy number alterations.
Main Results:
- ctDNA was detected in 18 out of 24 subjects.
- Subject-level concordance varied significantly by STS subtype: Leiomyosarcoma (LMS) 4/6, Undifferentiated Pleomorphic Sarcoma (UPS) 2/6, Dedifferentiated Liposarcoma (DDLPS) 1/6, Gastrointestinal Stromal Tumor (GIST) 0/6.
- Concordance for short variants with detectable tumor fraction was 76% (13/17), but copy number alterations showed poor concordance.
- LMS demonstrated the highest median tumor fraction and concordance.
Conclusions:
- Current commercial ctDNA panels show poor concordance with solid tumor CGP for many STS subtypes.
- ctDNA profiling in sarcoma may not be broadly applicable due to low concordance, particularly for copy number alterations.
- Further research with larger cohorts is needed to validate ctDNA utility in STS management.
