The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review

Our plain-English summary of The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review, by C. Fisher (Histopathology, 2014).

The study

• Author: C. Fisher
• Journal: Histopathology
• Published: 2014;64(1):134-50
• Type of article: Review
• Cited by: 126 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non-mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing-like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma-like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low-grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a 'promiscuous' gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.

© 2013 John Wiley & Sons Ltd.

In plain English

This article is a review of published research on soft tissue tumours that carry rearrangements of a gene called EWSR1. In these tumours, part of EWSR1 is joined to part of another gene, forming a new fusion gene. The author, of the Royal Marsden Hospital in London, described the tumour types in which such rearrangements have been reported. These include Ewing sarcoma, desmoplastic small round cell tumour, myxoid/round cell liposarcoma, clear cell sarcoma, myoepithelial tumours and rare examples of others. The article does not study asbestos. Its only discussion of mesothelioma summarises an earlier report of two mesothelioma cases with an EWSR1-YY1 fusion gene. Both tumours had epithelioid features; only one had detectable transcripts of the reverse-order fusion, YY1-EWSR1. The review does not say where in the body these mesotheliomas arose. The author concluded that EWSR1 rearrangement with different partner genes results in a variety of soft tissue tumours. In the author's view, diagnosis often needs a second genetic test (RT-PCR) alongside FISH, together with clinical and laboratory findings. The author noted that many reports concern few cases or single examples.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature
• Who was studied: No study population of its own. The author reviewed published reports on soft tissue tumours with EWSR1 gene rearrangements.
• Exposure: No asbestos or other environmental or occupational exposure is studied. The subject is EWSR1 gene rearrangements (fusion genes) in tumours.
• Main results:
  • Mesothelioma (as reported in an earlier publication the review cites): two cases of mesothelioma were described with an EWSR1-YY1 fusion gene. Only one had detectable YY1-EWSR1 transcripts, which is the reverse-order fusion.
  • Both of those mesotheliomas had epithelioid morphology and expressed the markers CK5/6 and calretinin. One was also WT1-positive.
  • Ewing sarcoma/PNET (summarised from other studies): the most common rearrangement, in about 85% of cases, gives an EWSR1-FLI1 fusion. A further 10% of tumours have an EWSR1-ERG fusion.
  • Soft tissue myoepithelial tumours (summarised from other studies): EWSR1 rearrangements have been described in about half.
  • Primary pulmonary myxoid sarcoma (from the author's group's earlier published series of 10 cases): metastasis occurred in two of the six patients with available follow-up.
• The authors' conclusion: The author concluded that EWSR1 rearrangement with different fusion partners results in a variety of soft tissue tumours. Because of this diversity, in many cases identifying fusion transcripts by RT-PCR is needed in addition to FISH, along with clinical and immunohistochemical correlation.
• Limitations the authors state:
  • Many of the reports reviewed concern few cases or single examples.

Topics

Medical terms in this study, explained in our Lexicon: Sarcoma, Translocation, Desmoplastic Mesothelioma, Epithelioid, Mesothelioma, Neoplasm.

Related studies

• RNA sequencing identifies fusion of the EWSR1 and YY1 genes in mesothelioma with t(14;22)(q32;q12) — I. Panagopoulos, J. Thorsen, et al. (2013)
• Application of markers in the diagnosis of soft tissue tumours — P.J. Roholl, A.S. De Jong, et al. (1985)
• Evaluation of RET Gene Rearrangement by Fluorescence In Situ Hybridization in Malignant Mesothelioma — S. Salvi, J.L. Ravetti, et al. (2018)
• Soft tissue sarcomas of vulva — I. Davos, M.R. Abell (1976)
• Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation — H. Sato, T. Hasegawa, et al. (1999)
• Two cases of secondary soft tissue sarcomas after radiotherapy and radiochemotherapy — C. Saggia, G. Forti, et al. (2004)

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