The
desmoplastic small round cell tumor (DSRCT) is a recently recognized type of primitive
sarcoma defined by a predilection for young males, aggressive clinical behavior, widespread abdominal serosal involvement, and a primitive histological appearance with prominent desmoplasia and striking divergent, multilineage differentiation. Previous cytogenetic case reports have identified a recurrent translocation, t(11;22) (p13;q12). We have characterized this translocation at the molecular level in a panel of five DSRCTs using a candidate gene approach. Southern blot analysis revealed recurrent rearrangement of both EWS, located at 22q12, and rearranged in other
tumor-specific translocations in
Ewing's sarcoma and
clear cell sarcoma, and of WT1, the gene at 11p13 involved in a subset of
Wilms' tumor. Consistent comigration of the rearranged EWS and WT1 bands in multiple
enzyme digests indicated fusion of the genomic sequences, presumably due to the translocation t(11;22) (p13;q12). Northern blotting showed aberrant EWS and WT1 transcripts of the same size, suggesting the presence of a chimeric
messenger RNA. This was confirmed by
reverse transcriptase polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 or 9 primers, which revealed single polymerase chain reaction products consistent with a junction of EWS exon 7 to WT1 exon 8. DSRCT thus represents the third primitive
sarcoma in which the EWS gene is involved and the first instance of recurrent rearrangement of a tumor suppressor gene, WT1, in a specific
tumor type. The different translocation partners of the EWS gene, all of which are putative or definite
transcription factor genes, may be responsible for the
biological differences between DSRCT,
Ewing's sarcoma, and
clear cell sarcoma.