| Written | 1999-05 | Christine Pérot |
| Laboratoire de Cytogenetique, Hopital Saint-Antoine, Paris, France |
| Identity |
| ICD-Topo | C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE |
| ICD-Morpho | 8806/3 Desmoplastic small round cell tumor |
| Atlas_Id | 5023 |
| Phylum | Soft Tissues::Desmoplastic small round cell tumor |
| 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 |
 | |
| Figure 1: t(11;22)(p13;q12) G- banding - Courtesy Galina Aldrete and Charles D. Bangs | |
| Cytogenetics Molecular | frequent additionnal abnormalities, sometimes complex |
 | |
| Figure 2: EWSR1 breakapart FISH of formalin-fixed paraffin-embedded section showing EWSR1 rearrangement - Courtesy Gail Aldrete and Charles D. Bangs | |
| 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 |
| Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor. |
| Antonescu CR, Gerald WL, Magid MS, Ladanyi M |
| Diagnostic molecular pathology : the American journal of surgical pathology, part B. 1998 ; 7 (1) : 24-28. |
| PMID 9646031 |
| 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 PH |
| The American journal of surgical pathology. 1996 ; 20 (4) : 406-412. |
| PMID 8604806 |
| Fusion of the EWS1 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 FJ 3rd |
| Medical and pediatric oncology. 1996 ; 27 (5) : 434-439. |
| PMID 8827070 |
| Translocation (11;22)(p13;q12): primary change in intra-abdominal desmoplastic small round cell tumor. |
| Biegel JA, Conard K, Brooks JJ |
| Genes, chromosomes & cancer. 1993 ; 7 (2) : 119-121. |
| PMID 7687454 |
| 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 |
| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1998 ; 16 (9) : 3028-3036. |
| PMID 9738572 |
| 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 J |
| The American journal of surgical pathology. 1991 ; 15 (6) : 499-513. |
| PMID 1709557 |
| 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 |
| Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (4) : 1028-1032. |
| PMID 7862627 |
| 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 (15) : 1973-1979. |
| PMID 9591781 |
| Desmoplastic small cell tumor: a report of three cases and a review of the literature. |
| Kretschmar CS, Colbach C, Bhan I, Crombleholme TM |
| Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 1996 ; 18 (3) : 293-298. |
| PMID 8689345 |
| Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. |
| Ladanyi M, Gerald W |
| Cancer research. 1994 ; 54 (11) : 2837-2840. |
| PMID 8187063 |
| 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 RS |
| Cancer genetics and cytogenetics. 1993 ; 69 (1) : 17-21. |
| PMID 8374894 |
| A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round-cell tumor. |
| Sawyer JR, Tryka AF, Lewis JM |
| The American journal of surgical pathology. 1992 ; 16 (4) : 411-416. |
| PMID 1314522 |
| Cytogenetic abnormalities in an intraabdominal desmoplastic small cell tumor. |
| Shen WP, Towne B, Zadeh TM |
| Cancer genetics and cytogenetics. 1992 ; 64 (2) : 189-191. |
| PMID 1486572 |
| Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a report of the CHAMP study group. |
| Vanni R, Fletcher CD, Sciot R, Dal Cin P, De Wever I, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Tallini G, Van Den Berghe H, Willén H |
| Histopathology. 2000 ; 37 (3) : 212-217. |
| PMID 10971696 |
| Detection of chimeric transcripts in desmoplastic small round cell tumor and related developmental tumors by reverse transcriptase polymerase chain reaction. A specific diagnostic assay. |
| de Alava E, Ladanyi M, Rosai J, Gerald WL |
| The American journal of pathology. 1995 ; 147 (6) : 1584-1591. |
| PMID 7495283 |
| Citation |
| This paper should be referenced as such : |
| Prot, C |
| Soft tissue tumors: Desmoplastic small round cell tumor |
| Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):158-159. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Tumors/desmoplasticID5023.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 2 ] |
| Genes | EWSR1 | WT1 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(11;22)(p13;q11) EWSR1/WT1 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:24:50 CEST 2017 |
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