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A Comprehensive Circulating Tumor DNA Assay for Detection of Translocation and Copy-Number Changes in Pediatric Sarcomas
Open accessAbstract
Most circulating tumor DNA (ctDNA) assays are designed to detect recurrent mutations. Pediatric sarcomas share few recurrent mutations but rather are characterized by translocations and copy-number changes. We applied Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for detection of translocations found in the most common pediatric sarcomas. We also applied ichorCNA to the combined off-target reads from our hybrid capture to simultaneously detect copy-number alterations (CNA). We analyzed 64 prospectively collected plasma samples from 17 patients with pediatric sarcoma. Translocations were detected in the pretreatment plasma of 13 patients and were confirmed by tumor sequencing in 12 patients. Two of these patients had evidence of complex chromosomal rearrangements in their ctDNA. We also detected copy-number changes in the pretreatment plasma of 7 patients. We found that ctDNA levels correlated with metastatic status and clinical response. Furthermore, we detected rising ctDNA levels before relapse was clinically apparent, demonstrating the high sensitivity of our assay. This assay can be utilized for simultaneous detection of translocations and CNAs in the plasma of patients with pediatric sarcoma. While we describe our experience in pediatric sarcomas, this approach can be applied to other tumors that are driven by structural variants.
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Broad plasma panels, CNA-based WGS, methylation-based assays, cfRNA approaches, and CTC-based strategies remain more exploratory or proof-of-concept in most sarcoma subtypes, particularly when applied to low-volume MRD or routine surveillance settings.
“In contrast, broad plasma panels, CNA-based WGS, methylation-based assays, cfRNA approaches, and CTC-based strategies remain more exploratory or proof-of-concept in most sarcoma subtypes, particularly when applied to low-volume MRD or routine surveillance settings [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ].”
From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [30]
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Metadata
- Authors
- Shah, A. T., Azad, T. D., Breese, M. R., Chabon, J. J., Hamilton, E. G., Straessler, K., Kurtz, D. M., Leung, S. G., Spillinger, A., Liu, H.-Y., Behroozfard, I. H., Wittber, F. M., Hazard, F. K., Cho, S.-J., Daldrup-Link, H. E., Vo, K. T., Rangaswami, A., Pribnow, A., Spunt, S. L., Lacayo, N. J., Diehn, M., Alizadeh, A. A., & Sweet-Cordero, E. A.
- Affiliations
- University of California, San Francisco (US)
- Stanford Medicine (US)
- 1Division of Hematology/Oncology, Department of Pediatrics, University of California San Francisco, San Fransisco, California.
- ORCID
- Shah, Avanthi Tayi
- Azad, Tej D.
- Breese, Marcus R.
- Chabon, Jacob J.
- Hamilton, Emily G.
- Kurtz, David M.
- Leung, Stanley G.
- Spillinger, Aviv
- Behroozfard, Inge H.
- Hazard, Florette K.
- Cho, Soo-Jin
- Daldrup-Link, Heike E.
- Vo, Kieuhoa T.
- Pribnow, Allison
- Spunt, Sheri L.
- Lacayo, Norman J.
- Diehn, Maximilian
- Alizadeh, Ash A.
- Sweet-Cordero, E. Alejandro
- Venue
- Molecular Cancer Therapeutics
- Published
- 2021-08-05
- Volume
- 20
- Issue
- 10
- Pages
- 2016-2025
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC9307079
- OpenAlex
- W3187847571
- Cited by
- 42
- References
- 46
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 12 · 2023: 10 · 2022: 5
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cancer Therapeutics (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- St. Baldrick's Research Fellowship Grant
- Alex's Lemonade Stand Foundation
- Frank A. Campini Foundation
- Doris Duke Clinical Research Mentorship Award
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD081123A)
- Child Health Research Institute
- Children's Oncology Group Solid Malignancy-Integrated Translational Science Center
- Lucile Packard Children's Hospital
- Helen Diller Family Comprehensive Cancer Center
- NIH S10 Shared Instrumentation Grant (S10OD018220)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- circulating tumor DNA, pediatric sarcoma, translocation, copy number alterations, liquid biopsy, CAPP-Seq, ichorCNA, structural variants, complex chromosomal rearrangements, plasma biomarkers, metastasis, relapse detection, hybrid capture sequencing
- MeSH terms
- Circulating Tumor DNA, Child, DNA, Neoplasm, Follow-Up Studies, Humans, Longitudinal Studies, Mutation, Neoplasm Recurrence, Local, Prognosis, Prospective Studies, Sarcoma, Translocation, Genetic, Biomarkers, Tumor, DNA Copy Number Variations, High-Throughput Nucleotide Sequencing
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