Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor Journal Article
| Authors: | Ladanyi, M.; Gerald, W. |
| Article Title: | Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor |
| Abstract: | 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(ll;22) (pl3;ql2). 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 22ql2, and rearranged in other tumor-specific translocations in Ewing's sarcoma and clear cell sarcoma, and of WT1, the gene at llpl3 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(ll;22) (pl3;ql2). 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. © 1994, American Association for Cancer Research. All rights reserved. |
| Keywords: | adolescent; adult; clinical article; human tissue; human cell; histopathology; case report; differential diagnosis; ewing sarcoma; sarcoma; thoracic neoplasms; gene rearrangement; molecular sequence data; gene fusion; chromosome translocation; base sequence; genes, tumor suppressor; clear cell sarcoma; desmoplastic small round cell tumor; chromosomes, human, pair 22; abdominal neoplasms; human; male; female; priority journal; article; support, non-u.s. gov't; translocation (genetics) |
| Journal Title: | Cancer Research |
| Volume: | 54 |
| Issue: | 11 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1994-06-01 |
| Start Page: | 2837 |
| End Page: | 2840 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 8187063 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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