Soft tissue tumors: Desmoplastic small round cell tumor

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

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PMID 10971696

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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PMID 1709557

A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round-cell tumor.

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PMID 1314522

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Translocation (11;22)(p13;q12): primary change in intra-abdominal desmoplastic small round cell tumor.

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PMID 7687454

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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PMID 7495283

Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.

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PMID 7862627

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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The American journal of surgical pathology. 1996 ; 20 (4) : 406-412.

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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.

Benjamin LE, Fredericks WJ, Barr FG, Rauscher FJ 3rd

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Desmoplastic small cell tumor: a report of three cases and a review of the literature.

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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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PMID 9646031

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.

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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/Genes/desmoplasticID5023.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Sep 24 21:09:17 2008

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