No EWS/FLI1 fusion transcripts in giant-cell tumors of bone

Giant-cell tumor of bone (GCT) is a locally aggressive neoplasm of unknown etiology and pathogenesis. Cytogenetically, no consistent chromosomal alter ations, apart from telomeric associations involving various chromosome ends , have been described. Recently, however, it was reported that by using hig hly sensitive nested RT-PCR, a high proportion of GCT displays chimeric EWS /FLII fusion transcripts, i.e., the molecular genetic feature previously kn own to be strongly associated with the Ewing family of tumors. Thus, we dec ided to perform single-step and nested RT-PCR analyses on fresh frozen samp les from 10 cases of GCT, all of which had also been subjected to cytogenet ic analysis. After short-term culturing, none of the samples displayed any t(11;22)(q24;q12), the translocation characteristically giving rise to the EWS1 FLII fusion, nor any other type of rearrangement of 11q24 or 22q12. Fu rthermore, in none of the cases did the RT-PCR analysis, whether single ste p or nested, result in products corresponding to a hybrid EWS/FLII transcri pt. On the basis of these results, we conclude that translocations leading to fusion of the EWS and FLII genes are not part of the pathogenesis of GCT . (C) 2001 Wiley-Liss, Inc.