| Identity |
| Other names | t(11;22)(p13;q11) in desmoplastic small round cell tumor |
| Clinics and Pathology |
| Phenotype / cell stem origin | thought to be of peritoneal blastomatous cell origin |
| Epidemiology | rare; mostly in childhood and adolescent males (mean age: 22 yrs; sex ratio: 4.7 M/1F) |
| Clinics | very aggressive tumor, located almost exclusively to the peritoneal surfaces of the abdomen with involvement of many abdominal organs; very rare localisations outside the abdominal cavity (thoracic, cranial or skeletal localisations) |
| Pathology | characterized by nested pattern of small poorly differenciated tumor cell growth surrounded by dense desmoplastic stroma and immunohistochemistrical trilineage coexpression: epithelial (cytokeratin, EMA), mesenchymatous (desmin, vimentin) and neural (NSE) |
| Treatment | surgery may be performed before intensive chemo and radiotherapy |
| Prognosis | very poor; 35% overall progression-free survival at 5 yrs; median survival of about 17 months, although tumors are responsive to aggressive therapy in some cases |
| Cytogenetics |
| Note | besides the specific t(11;22)(p13;q12), 2 variant translocations have been described |
| Cytogenetics Molecular | frequent additionnal abnormalities, sometimes complex |
| Variants | the variant translocations are (t(2;21;22)(p23;q22;q13) and t(11;17)(p13;q11.2) |
| Genes involved and Proteins |
| Gene Name | EWSR1 |
| Location | 22q12 |
| Dna / Rna | spans over 40 kb, 17 exons ; 2,4 kb mRNA |
| Protein | 656 amino acids; N-term gln-thr-pro-rich region; C-terminal proline rich region; wide expression; RNA binding protein |
| Gene Name | WT1 |
| Location | 11p13 |
| Dna / Rna | spans over 50 kb, 10 exons; alternative splicings (in particular, the second site adds or remove 3 amino-acids (KTS) between the second and third zinc fingers and generates 2 isoforms); mRNA 3,5 kb |
| Protein | 52-54 Kda; 4 Cys2-His2 zinc fingers, glutamine- proline-glycine-rich transcriptional regulation domain, interacting with p53; nuclear localisation; transcriptional repressor |
| Result of the chromosomal anomaly |
| Hybrid Gene | |
| Description | 5'EWS- 3'WT1 |
| Transcript | mRNA detectable by RT-PCR (99% of DSRCT) |
| Fusion Protein | |
| Description | the N-term trans activation domain of EWS (exon 7) is fused to the C-term zinc fingers domain of WT1(exon 8); molecular variants have been described (exons 9 or 10 of EWS); transcritional activator ; the 2 isoforms EWS-WT1 without KTS and EWS-WT1 with KTS having different properties |
| Expression Localisation | nuclear |
| Oncogenesis | early: in the embryonal mesenchyme of the coelomic cavities; due to inapopriate transcriptional activition of WT1- responsive genes; the EWS-WT1 without KTS isoform would be dominantly acting as an oncogene |
| Bibliography |
| Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals. |
| Gerald WL, Miller HK , Battifora H, Miettinen M, Silva EG, Rosai JR. |
| Am J Surg Pathol 1991; 15: 499-513. |
| PMID 91233976 |
| A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intra-abdominal desmoplastic small round-cell tumor. |
| Sawyer JR, Tryka AF, Lewis JM. |
| Am J Surg Pathol 1992; 16: 411-416. |
| PMID 92231001 |
| Cytogenetic abnormalities in an intra-abdominal desmoplastic small round-cell tumor. |
| Violet Shen WP, Towne B, Zadeh T.M. |
| Cancer Genet Cytogenet 1992; 64: 189-191. |
| PMID 93137220 |
| Translocation (11;22)(p13;q12) : primary change in intra-abdominal desmoplastic small round-cell tumor. |
| Biegel JA, Conard K, Brooks JJ. |
| Genes Chromosom Cancer 1993; 7: 119-121. |
| PMID 93326523 |
| A recurring translocation, t(11;22)(p13;q11.2), characterizes intra-abdominal desmoplastic small round-cell tumors. |
| Rodriguez E, Sreekantaiah C, Gerald W, Reuter VE, Motzer RJ, Chaganti RSK. |
| Cancer Genet Cytogenet 1993; 69: 17-21. |
| PMID 93386675 |
| Fusion of the EWS and WT1 genes in the desmoplastic small round-cell tumor. |
| Ladanyi M, Gerald W. |
| Cancer Res 1994; 54: 2837-2840. |
| PMID 94243792 |
| Detection of chimeric transcripts in desmoplastic small round cell tumor and related tumors by reverse transcriptase polymerase chain reaction. |
| de Alava E, Ladanyi M, Rosai J, Gerald W. |
| Am J Pathol 1995; 147: 1584-159. |
| PMID 96094742 |
| Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. |
| Gerald WL, Rosai J, Ladanyi M. |
| Proc Natl Acad Sci USA 1995; 92 : 1028-1032. |
| PMID 95166761 |
| Detection of the EWS/WT1 gene fusion by reverse transcriptase-polymerase chain reaction in the diagnosis of intra-abdominal desmoplastic small round cell tumor. |
| Argatoff LH, O'Connell JX, Mathers JA, Gilks CB, Sorensen PHB. |
| Am J Surg Pathol 1996; 20: 406-412. |
| PMID 96183388 |
| Fusion of the EWS and WT1 genes as a result of the t(11;22)(p13;q12) translocation in desmoplastic small round cell tumors. |
| Benjamin LE, Fredericks WJ, Barr FG, Rauscher III FJ. |
| Med Pediatr Oncol, 1996; 27: 434-439. |
| PMID 96424609 |
| Desmoplastic small cell tumor : a report of three cases and a review of the literature. |
| Kretschmar CS, Colbach C, Bhan I, Crombleholme TM. |
| J Pediatr Hematol Oncol 1996; 18: 293-298. |
| PMID 96300289 |
| Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor. |
| Antonescu CR, Gerald WL, Magid MS, Ladanyi M. |
| Diagn Mol Pathol 1998; 7: 24-28. |
| PMID 98309999 |
| Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22) (p13;q12) : desmoplastic small round-cell tumor and its variants. |
| Gerald WL, Ladanyi M, de Alava E, Cuatrecasas M, Kushner BH, LaQuaglia MP, Rosai J. |
| J Clin Oncol 1998; 16: 3028-3036. |
| PMID 98408952 |
| The desmoplastic small round cell tumor t(11;22) translocation produces EWS/WT1 isoforms with differing oncogenic properties. |
| Kim J, Lee K, Pelletier J. |
| Oncogene 1998; 16: 1973-1977. |
| PMID 98252455 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 05-1999 | Christine Pérot |
| Citation |
| This paper should be referenced as such : |
| Pérot C . Soft tissue tumors: Desmoplastic small round cell tumor. Atlas Genet Cytogenet Oncol Haematol. May 1999 . URL : http://AtlasGeneticsOncology.org/Tumors/desmoplasticID5023.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Apr 17 14:14:56 2008 |
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