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

Transl Res. 2018 Nov;201:136-153. doi: 10.1016/j.trsl.2018.05.007. Epub 2018 Jun 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / therapy
  • Exosomes*
  • Extracellular Vesicles / physiology
  • Humans
  • Liquid Biopsy / methods*
  • Microfluidic Analytical Techniques
  • Oncogene Proteins, Fusion / genetics
  • Proto-Oncogene Protein c-fli-1 / genetics
  • RNA-Binding Protein EWS / genetics
  • Sarcoma, Ewing / diagnosis
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / pathology*
  • Sarcoma, Ewing / therapy
  • Translocation, Genetic


  • EWS-FLI fusion protein
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS