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Cited by 52Sarcoma Diagnosis and TreatmentCancer Genomics and DiagnosticsChromatin Remodeling and Cancer

Plasma DNA-Based Molecular Diagnosis, Prognostication, and Monitoring of Patients With EWSR1 Fusion-Positive Sarcomas

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Shukla, Neerav N., Patel, Juber A., Magnan, Heather, Zehir, Ahmet, You, Daoqi, Tang, Jiabin, Meng, Fanli, Samoila, Aliaksandra +9 more·2017·JCO Precision Oncology
DOI 10.1200/po.16.00028PMC PMC5881916
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Abstract

Purpose: Ewing sarcoma (ES) and desmoplastic small round cell tumors (DSRCTs) are aggressive sarcomas molecularly characterized by EWSR1 gene fusions. As pathognomonic genomic events in these respective tumor types, EWSR1 fusions represent robust potential biomarkers for disease monitoring. Methods: To investigate the feasibility of identifying EWSR1 fusions in plasma-derived cell-free DNA (cfDNA) from patients with ES and DSRCT, we evaluated two complementary approaches in samples from 17 patients with radiographic evidence of disease. The first approach involved identification of patient-specific genomic EWSR1 fusion breakpoints in formalin-fixed, paraffin-embedded tumor DNA using a broad, hybridization capture-based next-generation sequencing (NGS) panel, followed by design of patient-specific droplet digital polymerase chain reaction (ddPCR) assays for plasma cfDNA interrogation. The second approach used a disease-tailored targeted hybridization capture-based NGS panel applied directly to cfDNA, which included EWSR1 as well as several other genes with potential prognostic use. Results: EWSR1 fusions were identified in 11 of 11 (100%) ES and five of six (83%) DSRCT cfDNA samples by ddPCR, whereas 10 of 11 (91%) and four of six (67%) were identified by NGS. The ddPCR approach had higher sensitivity, ranging between 0.009% and 0.018%. However, the hybrid capture–based NGS assay identified the precise fusion breakpoints in the majority of cfDNA samples, as well as mutations in TP53 and STAG2, two other recurrent, clinically significant alterations in ES, all without prior knowledge of the tumor genotype. Conclusion: These results provide a compelling rationale for an integrated approach using both NGS and ddPCR for plasma cfDNA-based biomarker evaluations in prospective cooperative group studies.

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  • 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 [23]

  • In Ewing sarcoma and other breakpoint-defined tumors, the disease-defining structural variant provides a stable and highly specific target for longitudinal monitoring.

    “In Ewing sarcoma and other breakpoint-defined tumors, the disease-defining structural variant provides a stable and highly specific target for longitudinal monitoring [ 13 , 22 , 23 ].”

    From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [23]

  • Ewing sarcoma and other translocation-associated sarcomas provide a different model because disease-defining structural variants can serve as highly specific molecular targets for longitudinal monitoring.

    “Ewing sarcoma and other translocation-associated sarcomas provide a different model because disease-defining structural variants can serve as highly specific molecular targets for longitudinal monitoring [ 13 , 22 , 23 ].”

    From Signals Alongside Scans: A Genomics-Guided Framework for Liquid Biopsy in Bone and Soft-Tissue Sarcomas (2026) · cites this paper as [23]

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2 of the 39 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [10]Zoubek A Ladenstein R Windhager R Predictive potential of testing for bone marrow involvement in Ewing tumor patients by RT-PCR: a preliminary evaluation Int J Cancer 1998 79 56 60 9495359
  2. [29]de Alava E Antonescu CR Panizo A Prognostic impact of P53 status in Ewing sarcoma Cancer 2000 89 783 92 10951341
  3. [32]Wei G Antonescu CR de Alava E Prognostic impact of INK4A deletion in Ewing sarcoma Cancer 2000 89 793 9 10951342

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Authors
Shukla, N. N., Patel, J. A., Magnan, H., Zehir, A., You, D., Tang, J., Meng, F., Samoila, A., Slotkin, E. K., Ambati, S. R., Chou, A. J., Wexler, L. H., Meyers, P. A., Peerschke, E. I., Viale, A., Berger, M. F., & Ladanyi, M.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Shukla, Neerav N.
ORCID
Venue
JCO Precision Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2017-11
Volume
2017
Issue
1
Pages
1-11
ISSN
2473-4284 (ISSN-L)
DOI
10.1200/po.16.00028
PMC
PMC5881916
OpenAlex
W2619646140
Cited by
52
References
39
Citations by year
2026: 4 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 3
FWCI
5.43
Type
journal article
Language
en
Open access
Locations
  • JCO Precision Oncology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (P30CA008748)
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
Ewing sarcoma, desmoplastic small round cell tumor, plasma cell-free DNA, liquid biopsy, droplet digital PCR, hybridization capture sequencing, TP53 mutation, STAG2 mutation, prognostic factors, disease surveillance

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