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Soft tissue tumors: Desmoplastic small round cell tumor

Identity

Phylum Soft Tissue Tumors:Uncertain differentiation:Desmoplastic small round cell tumor
Other namest(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
  

Other genes implicated (Data extracted from papers in the Atlas)

Genes EWSR1 WT1

Bibliography

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Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals.
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A recurring translocation, t(11;22)(p13;q11.2), characterizes intra-abdominal desmoplastic small round-cell tumors.
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Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor.
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Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.
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Detection of the EWS/WT1 gene fusion by reverse transcriptase-polymerase chain reaction in the diagnosis of intra-abdominal desmoplastic small round cell tumor.
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Fusion of the EWS1 and WT1 genes as a result of the t(11;22)(p13;q12) translocation in desmoplastic small round cell tumors.
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Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor.
Antonescu CR, Gerald WL, Magid MS, Ladanyi M
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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
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The desmoplastic small round cell tumor t(11;22) translocation produces EWS/WT1 isoforms with differing oncogenic properties.
Kim J, Lee K, Pelletier J
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Contributor(s)

Written05-1999Christine Pérot

Citation

This paper should be referenced as such :
Pérot C . Soft tissue tumors: Desmoplastic small round cell tum. Atlas Genet Cytogenet Oncol Haematol. May 1999 .
URL : http://AtlasGeneticsOncology.org/Tumors/desmoplasticID5023.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37544/1/05-1999-desmoplasticID5023.pdf   [ Bibliographic record ]

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