Cryptic exons as a source of increased diversity of Ewing tumor-associatedEWS-FLI1 chimeric products

In the Ewing family of tumors (EFT), the EWS gene is rearranged with member s of the ets oncogene family. Variability in genomic breakpoint locations i s the source of significant heterogeneity in fusion product structure. As a consequence of variably included exon sequences from the two partner genes , a variable amount of additional peptide sequence is inserted in between t he minimal transforming domains. Some of this molecular diversity has recen tly been correlated with disparate clinical outcome. Here we report on cryp tic exons found in the chimeric RNA of three EFT with different EWS-FLI1 fu sions, In two tumors, the emergence of a cryptic exon from FLI1 intron 5 in the chimeric RNA was apparently unrelated to the genomic rearrangement tha t occurred in FLI1 introns 4 and 5, respectively, In one case, a novel exon was generated through the creation of an artificial splice acceptor site i n FLI1 intron 6 by the genomic rearrangement that occurred in EWS intron 8. These results further extend the spectrum of molecular diversity in EFT. ( C) 1999 Academic Press.