MOLECULAR ANALYSIS OF A T(11-22) TRANSLOCATION JUNCTION IN A CASE OF EWINGS-SARCOMA

Polymerase chain reaction (PCR)-directed sequence analysis was perform ed to characterize the genomic and cDNA breakpoint junctions of t(11;2 2) (q24;q 12) translocation in a case of Ewing's sarcoma, in which the EWS gene located on chromosome 22 is rearranged with the FLI1 gene lo cated on chromosome 11. RNA-PCR revealed the novel chimeric product of EWS/FLI1 gene on the derivative chromosome (der) 22, resulting from a probable fusion of EWS exon 7 to FLI1 exon 9. Sequencing of the PCR-a mplified genomic fragments of the fusion genes showed that the breakpo ints on der(22) occurred in EWS intron 7 and, most probably, in FLI1 i ntron 8. Those of the untranscribed counterpart on der(11) were locate d in the same FLI1 intron and in EWS exon 11, with deletion of a consi derable amount of sequences from both genes. These findings indicate a symmetric junction at the molecular level in the present t(11;22). Non e of the reported conserved sequences that mediate other cancer chromo some translocations was observed around the genomic junctions. Instead , a palindromic hexamer 5'-GCTAGC-3' was found to flank the breakpoint s of both genes on der(22), which may have a functional significance i n the genesis of the t(11;22). (C) 1995 Wiley-Liss, Inc.