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Molecular assessment of circulating exosomes toward liquid biopsy diagnosis of Ewing sarcoma family of tumors

  • Peng Zhang
    Correspondence
    Reprint requests: Andrew K. Godwin and Yong Zeng, Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr, Lawrence KS 66045.
    Affiliations
    Department of Chemistry, University of Kansas, Lawrence, Kansas
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  • Glenson Samuel
    Correspondence
    Reprint requests: Andrew K. Godwin and Yong Zeng, Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr, Lawrence KS 66045.
    Affiliations
    Division of Hematology, Oncology and Bone Marrow Transplant, Children's Mercy Hospitals & Clinics, Kansas City, Missouri
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  • Jennifer Crow
    Affiliations
    Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas
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  • Andrew K. Godwin
    Correspondence
    Reprint requests: Andrew K. Godwin and Yong Zeng, Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr, Lawrence KS 66045.
    Affiliations
    Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas

    University of Kansas Cancer Center, Kansas City, Kansas
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  • Yong Zeng
    Correspondence
    Reprint requests: Andrew K. Godwin and Yong Zeng, Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr, Lawrence KS 66045.
    Affiliations
    Department of Chemistry, University of Kansas, Lawrence, Kansas

    University of Kansas Cancer Center, Kansas City, Kansas
    Search for articles by this author
      Ewing sarcoma was first described in 1921 in the Proceedings of the New York Pathological Society by an eminent American pathologist from Cornell named James R. Ewing as a “diffuse endothelioma of bone.” Since this initial description, more has been discovered regarding Ewing sarcoma and in the 1980’s both Ewing sarcoma and peripheral primitive neuroectodermal tumors due to their similar features and shared identical genetic abnormality were grouped into a class of cancers entitled Ewing sarcoma family of tumors (ESFTs). Ewing sarcoma is the second most common pediatric osseous malignancy followed by osteosarcoma, with highest incidence among 10–20 years old. Ewing sarcoma is consistently associated with chromosomal translocation and functional fusion of the EWSR1 gene to any of several structurally related transcription factor genes of the E26 transformation-specific family. These tumor-specific molecular rearrangements are useful for primary diagnosis, may provide prognostic information, and present potential therapeutic targets. Therefore, ways to rapidly and efficiently detect these defining genomic alterations are of clinical relevance. Within the past decade, liquid biopsies including extracellular vesicles (EVs), have emerged as a promising alternative and/or complimentary approach to standard tumor biopsies. It was recently reported that fusion mRNAs from tumor-specific chromosome translocations can be detected in Ewing sarcoma cell-derived exosomes. Within this review, we overview the current advances in Ewing sarcoma and the opportunities and challenges in exploiting circulating exosomes, primarily small bioactive EVs (30–180 nm), as developing sources of biomarkers for diagnosis and therapeutic response monitoring in children and young adult patients with ESFT.

      Abbreviations:

      ESFT (Ewing sarcoma Family of tumors), EVs (extracellular vesicles), PNET (peripheral primitive neuroectodermal tumor), ETS (E26 transformation-specific), FDG (2-deoxy-2-[fluorine-18]fluoro-D-glucose), SEC (size-exclusion chromatography), CTCs (circulating tumor cells), AUC, (area under curve)
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