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Cellular Oncology

, Volume 36, Issue 3, pp 191–200 | Cite as

Multiple splice variants of EWSR1-ETS fusion transcripts co-existing in the Ewing sarcoma family of tumors

  • Barbara PatócsEmail author
  • Krisztina Németh
  • Miklós Garami
  • Gabriella Arató
  • Ilona Kovalszky
  • Miklós Szendrői
  • György Fekete
Original Paper

Abstract

Purpose

The Ewing sarcoma family of tumors (EFT) is characterized by fusions of the EWSR1 gene on chromosome 22q12 with either one of the genes encoding members of the ETS family of transcription factors, in the majority of cases FLI1 or ERG. Many alternative EWSR1-ETS gene fusions have been encountered, due to variations in the locations of the EWSR1 and ETS genomic breakpoints. The resulting heterogeneity in EWSR1-ETS fusion transcripts may further be increased by the occurrence of multiple splice variants within the same tumor. Here we present a retrospective study designed to detect all of the EWSR1-FLI1 and EWSR1-ERG fusion transcripts in a series of 23 fresh frozen EFT tissues.

Methods

RT-PCR and nested fluorescent multiplex PCR were used to amplify EWSR1-FLI1 and EWSR1-ERG transcripts from EFT tissues. Fusion transcripts were identified by laser-induced fluorescent capillary electrophoresis and confirmed by sequence analysis.

Results

Nine different EWSR1-FLI1 fusion transcripts and one EWSR1-ERG fusion transcript were identified in 21 out of 23 fresh frozen EFT tissue samples. In five cases multiple fusion transcripts were found to coexist in the same tumor sample. We additionally reviewed previous reports on twelve cases with multiple EWSR1-ETS fusion transcripts.

Conclusions

Alternative splicing may frequently affect the process of EFT-associated fusion gene transcription and, as such, may significantly contribute to the pathogenic role of EFT-associated chromosome translocations. In a considerable number of cases this may result in multiple splice variants within the same tumor.

Keywords

Ewing sarcoma family of tumors EWSR1 gene fusions Alternative splicing Molecular diagnostics 

Notes

Acknowledgments

The authors would like to thank Prof. Dezső Schuler for critical reading of the manuscript, Tibor Fülep and Dr. Ilona Milánkovics for their helpful suggestions and Krisztina Staub and Zsoltné Vincze for their technical assistance.

Disclosure/Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© International Society for Cellular Oncology 2013

Authors and Affiliations

  • Barbara Patócs
    • 1
    Email author
  • Krisztina Németh
    • 1
  • Miklós Garami
    • 1
  • Gabriella Arató
    • 2
  • Ilona Kovalszky
    • 3
  • Miklós Szendrői
    • 4
  • György Fekete
    • 1
  1. 1.2nd Department of PaediatricsSemmelweis UniversityBudapestHungary
  2. 2.Department of PathologySzent János HospitalBudapestHungary
  3. 3.1st Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
  4. 4.Department of OrthopaedicsSemmelweis UniversityBudapestHungary

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