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Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data.
Ewing tumours (ET), including Ewing's sarcoma and peripheral primitive neuroectodermal tumour, are well characterised at the molecular level by a unique chromosomal rearrangement which fuses the EWS gene to one of two closely related ETS proto-oncogenes, FLI-1 or ERG. Expression of the resultin...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1994
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033557/ https://www.ncbi.nlm.nih.gov/pubmed/7524604 |
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author | Zoubek, A. Pfleiderer, C. Salzer-Kuntschik, M. Amann, G. Windhager, R. Fink, F. M. Koscielniak, E. Delattre, O. Strehl, S. Ambros, P. F. |
author_facet | Zoubek, A. Pfleiderer, C. Salzer-Kuntschik, M. Amann, G. Windhager, R. Fink, F. M. Koscielniak, E. Delattre, O. Strehl, S. Ambros, P. F. |
author_sort | Zoubek, A. |
collection | PubMed |
description | Ewing tumours (ET), including Ewing's sarcoma and peripheral primitive neuroectodermal tumour, are well characterised at the molecular level by a unique chromosomal rearrangement which fuses the EWS gene to one of two closely related ETS proto-oncogenes, FLI-1 or ERG. Expression of the resulting chimaeric transcripts can be readily detected by reversed transcriptase polymerase chain reaction (RT-PCR). This approach led to the identification of a number of different exon combinations at the junction site of coding sequences. The physiological consequences of the observed variability in the hinge region of EWS chimaeric proteins are not known. We have analysed tumour-derived material from 30 ET patients with well-documented clinical course (18 with localised and 12 with metastatic disease at diagnosis) for the presence of EWS/FLI-1 or EWS/ERG RNA. Karyotypes were obtained in 21 out of 27 cases and analysed by routine cytogenetics. A chromosome 22 rearrangement was demonstrated in 18 cases (67%). In contrast, RT-PCR revealed the presence of chimaeric transcripts in 28 tumours (93%), with fusions of EWS exon 7 to FLI-1 exons 6 (19/28), 5 (4/28) and 7 (1/28). In addition, EWS/FLI-1 exon combinations 10/5 and 9/4 were observed in one case each. In the last tumour, the presence of at least four additional splicing variants corresponding to fusion of EWS exon 7 to FLI-1 exons 4, 6, 8 and 9 was demonstrated. Two tumours expressed EWS/ERG fusion transcripts involving EWS exon 7 and ERG exon 6. In this study, EWS/FLI-1 exon combinations 7/6 (type I) predominated over 7/5 (type II) in localised ET (14 versus 1) and were more abundant in tumours affecting the long bones (9 versus 0), whereas in central axis tumours and metastatic disease there was only little difference in the frequency of the two types. So far, no correlations between different chimaeric EWS transcripts and any other clinical parameters have been identified. IMAGES: |
format | Text |
id | pubmed-2033557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1994 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20335572009-09-10 Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. Zoubek, A. Pfleiderer, C. Salzer-Kuntschik, M. Amann, G. Windhager, R. Fink, F. M. Koscielniak, E. Delattre, O. Strehl, S. Ambros, P. F. Br J Cancer Research Article Ewing tumours (ET), including Ewing's sarcoma and peripheral primitive neuroectodermal tumour, are well characterised at the molecular level by a unique chromosomal rearrangement which fuses the EWS gene to one of two closely related ETS proto-oncogenes, FLI-1 or ERG. Expression of the resulting chimaeric transcripts can be readily detected by reversed transcriptase polymerase chain reaction (RT-PCR). This approach led to the identification of a number of different exon combinations at the junction site of coding sequences. The physiological consequences of the observed variability in the hinge region of EWS chimaeric proteins are not known. We have analysed tumour-derived material from 30 ET patients with well-documented clinical course (18 with localised and 12 with metastatic disease at diagnosis) for the presence of EWS/FLI-1 or EWS/ERG RNA. Karyotypes were obtained in 21 out of 27 cases and analysed by routine cytogenetics. A chromosome 22 rearrangement was demonstrated in 18 cases (67%). In contrast, RT-PCR revealed the presence of chimaeric transcripts in 28 tumours (93%), with fusions of EWS exon 7 to FLI-1 exons 6 (19/28), 5 (4/28) and 7 (1/28). In addition, EWS/FLI-1 exon combinations 10/5 and 9/4 were observed in one case each. In the last tumour, the presence of at least four additional splicing variants corresponding to fusion of EWS exon 7 to FLI-1 exons 4, 6, 8 and 9 was demonstrated. Two tumours expressed EWS/ERG fusion transcripts involving EWS exon 7 and ERG exon 6. In this study, EWS/FLI-1 exon combinations 7/6 (type I) predominated over 7/5 (type II) in localised ET (14 versus 1) and were more abundant in tumours affecting the long bones (9 versus 0), whereas in central axis tumours and metastatic disease there was only little difference in the frequency of the two types. So far, no correlations between different chimaeric EWS transcripts and any other clinical parameters have been identified. IMAGES: Nature Publishing Group 1994-11 /pmc/articles/PMC2033557/ /pubmed/7524604 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Zoubek, A. Pfleiderer, C. Salzer-Kuntschik, M. Amann, G. Windhager, R. Fink, F. M. Koscielniak, E. Delattre, O. Strehl, S. Ambros, P. F. Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. |
title | Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. |
title_full | Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. |
title_fullStr | Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. |
title_full_unstemmed | Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. |
title_short | Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. |
title_sort | variability of ews chimaeric transcripts in ewing tumours: a comparison of clinical and molecular data. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2033557/ https://www.ncbi.nlm.nih.gov/pubmed/7524604 |
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