Clinics and Pathology
Phenotype stem cell 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
Figure 1: t(11;22)(p13;q12) G- banding - Courtesy Galina Aldrete and Charles D. Bangs
Note
besides the specific t(11;22)(p13;q12), 2 variant translocations have been described
Figure 2: EWSR1 breakapart FISH of formalin-fixed paraffin-embedded section showing EWSR1 rearrangement - Courtesy Gail Aldrete and Charles D. Bangs
Additional anomalies
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 (Ewing sarcoma breakpoint region 1)
Location
22q12.2
Dna rna description
spans over 40 kb, 17 exons ; 2,4 kb mRNA
Protein description
656 amino acids; N-term gln-thr-pro-rich region; C-terminal proline rich region; wide expression; RNA binding protein
Gene name
WT1 (Wilms tumor suppressor gene)
Location
11p13
Dna rna description
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 description
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
Description
5EWS- 3WT1
Transcript
mRNA detectable by RT-PCR (99% of DSRCT)
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
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9646031 | 1998 | Molecular variants of the EWS-WT1 gene fusion in desmoplastic small round cell tumor. | Antonescu CR et al |
| 8604806 | 1996 | 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 et al |
| 8827070 | 1996 | 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 et al |
| 7687454 | 1993 | Translocation (11;22)(p13;q12): primary change in intra-abdominal desmoplastic small round cell tumor. | Biegel JA et al |
| 9738572 | 1998 | Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. | Gerald WL et al |
| 1709557 | 1991 | 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 et al |
| 7862627 | 1995 | Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. | Gerald WL et al |
| 9591781 | 1998 | The desmoplastic small round cell tumor t(11;22) translocation produces EWS/WT1 isoforms with differing oncogenic properties. | Kim J et al |
| 8689345 | 1996 | Desmoplastic small cell tumor: a report of three cases and a review of the literature. | Kretschmar CS et al |
| 8187063 | 1994 | Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. | Ladanyi M et al |
| 8374894 | 1993 | A recurring translocation, t(11;22)(p13;q11.2), characterizes intra-abdominal desmoplastic small round-cell tumors. | Rodriguez E et al |
| 1314522 | 1992 | A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round-cell tumor. | Sawyer JR et al |
| 1486572 | 1992 | Cytogenetic abnormalities in an intraabdominal desmoplastic small cell tumor. | Shen WP et al |
| 10971696 | 2000 | Cytogenetic evidence of clonality in cutaneous benign fibrous histiocytomas: a report of the CHAMP study group. | Vanni R et al |
| 7495283 | 1995 | 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 et al |
Citation
Christine Pérot
Soft Tissues: Desmoplastic small round cell tumor
Atlas Genet Cytogenet Oncol Haematol. 1999-05-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5023/soft-tissues-desmoplastic-small-round-cell-tumor
