Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1994-11

AUTHORS

A Zoubek, C Pfleiderer, M Salzer-Kuntschik, G Amann, R Windhager, FM Fink, E Koscielniak, O Delattre, S Strehl, PF Ambros, H Gadner, H Kovar

ABSTRACT

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. More... »

PAGES

908-913

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bjc.1994.419

DOI

http://dx.doi.org/10.1038/bjc.1994.419

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1013942483

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/7524604


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