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van der Ent et al. J Transl Genet Genom 2018;2:10 Journal of Translational
DOI: 10.20517/jtgg.2018.09 Genetics and Genomics

Review Open Access

Molecular genetics of Ewing sarcoma, model
systems and finding novel (immuno-) therapeutic

targets

Wietske van der Ent , Laurens G.L. Sand , Pancras C.W. Hogendoorn 3
2
1
1 Institute of Biology, Leiden University, Leiden 2311 EZ, The Netherlands.
2 Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
3 Department of Pathology, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.

Correspondence to: Prof. Pancras C.W. Hogendoorn, Department of Pathology, Leiden University Medical Center, Albinusdreef 2,
Leiden 2333 ZA, The Netherlands. E-mail: p.c.w.hogendoorn@lumc.nl
How to cite this article: van der Ent W, Sand LGL, Hogendoorn PCW. Molecular genetics of Ewing sarcoma, model systems and finding
novel (immuno-) therapeutic targets. J Transl Genet Genom 2018;2:10. https://doi.org/10.20517/jtgg.2018.09

Received: 11 May 2018 First Decision: 15 May 2018 Revised: 20 May 2018 Accepted: 21 May 20188 Published: 16 Jul 2018

Science Editor: David N. Cooper Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

Abstract
Ewing sarcoma (EWS) is a bone- and soft tissue tumour affecting primarily children and young adults. A quarter of
patients present with metastases at the time of diagnosis and have a poor outlook in terms of overall survival. Efforts
are made across the field to gain deeper insight in the genetics of this enigmatic neoplasm. EWS is characterized by
presence of an oncogenic translocation gene, EWSR1-ETS. In addition, there are a limited number of known recurrent
DNA copy number variations and mutations. Subsequent of the above, the epigenetic profile of EWS is subject of interest.
In this review, we summarize the current available knowledge on the genetics underpinning EWS, explore the current
knowledge of its epigenetic profile, discuss in vitro and in vivo model systems, and explore the unravelling knowledge of
potential targets for treatment including recent insights into potential immunotherapy.

Keywords: Bone neoplasm, Ewing sarcoma, genetic translocation, DNA copy number variation, mutation

INTRODUCTION
Ewing sarcoma (EWS) is the second most common bone- and soft tissue sarcoma affecting children and
young adults. It presents microscopically as a tumour consisting of rather uniform small blue round cells
expressing CD99 on its cell membrane, usually with glycogen deposition in its cytoplasm, and is character-
ized by an EWSR1-ETS translocation. Peak incidence is between 10 and 20 years old, with a slight majority
[1]
of male patients (1.4:1 ratio) . EWS was first described by James Ewing in 1921 as a “diffuse endothelioma
[2]
of bone” , however, the cell of origin of EWS has long been a subject of debate. Based on ultrastructural
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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