<b>Purpose:</b> Desmoplastic small round cell tumor (DSRCT), which harbors EWSR1-WT1 t(11;22)(p13:q12) chromosomal translocation, is an aggressive malignancy that typically presents as intra-abdominal sarcomatosis in young males.
In the new review all the tumors were re-classified as, ES (n=16), Ewing-like tumor with EWSR1 rearrangement and amplification and possible EWSR1-NFATC2 gene fusion (n=1), CIC-rearranged sarcomas or undifferentiated sarcoma, most consistent with CIC-rearranged sarcoma (n=7), sarcoma with BCOR-alteration or undifferentiated sarcoma, consistent with BCOR-associated sarcoma (n=3), neuroblastoma (n=2), unclassifiable neoplasm with neuroblastic differentiation (n=1), malignant rhabdoid tumor (n=2), lymphoblastic lymphoma (n=1), clear cell sarcoma of the gastrointestinal tract (n=1), small cell carcinoma (n=1), sclerosing rhabdomyosarcoma (n=1), desmoplastic small round cell tumor (n=1), malignant peripheral sheath nerve tumor (n=1), poorly-differentiated synovial sarcoma (n=1), Possible gastrointestinal stromal tumor/GIST with predominant round cells (n=1) and possible SMARCA4-deficient-sarcoma (n=1).
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1).
EWSR1 rearrangements were first identified in Ewing sarcoma, but the spectrum of EWSR1-rearranged neoplasms now includes many soft tissue tumour subtypes including desmoplastic small round cell tumour (DSRCT), myxoid liposarcoma (MLPS), extraskeletal myxoid chondrosarcoma (EMC), angiomatoid fibrous histiocytoma (AFH), clear cell sarcoma (CCS) and myoepithelial neoplasms.
Using JN-DSRCT-1, a cell line derived from DSRCT expressing the EWS-WT1 fusion protein, we investigated the ability of trabectedin to modify the function of the chimeric protein, as in other sarcomas expressing fusion proteins.
Here we present a strategy combining CRISPR-Cas9 technology and homology-directed repair to allow for the selection of human mesenchymal stem cells harboring the oncogenic translocation <i>EWSR1-WT1</i> found in the aggressive desmoplastic small round cell tumor.
Three cases (1.5%) revealed the SYT-SSX transcript for Synovial sarcoma, and one (0.5%) a EWSR1-WT1 transcript for Desmoplastic Small Round Cell tumor.
In these challenging cases, detection of an EWSR1-WT1 rearrangement and selective WT1 carboxy-terminus immunoreactivity (characteristic of DSRCT) or dual immunoreactivity for the WT1 amino-terminus and carboxy-terminus (characteristic of WT) remain the most discriminating diagnostic tools.
We found disagreement in only three samples: one ES/pPNET and one embryonal rhabdomyosarcoma harbor a PAX3-FOXO1 translocation (for ARMS), and one neuroepithelioma harboring a EWS-WT1 (for DSRCT).
Fluorescence in situ hybridization studies using an EWSR1 break-apart probe confirmed the presence of a rearrangement involving the EWSR1 locus and RT-PCR demonstrated the presence of an EWSR1-WT1 fusion transcript associated with the t(11;22) rearrangement, which supported a diagnosis of DSRCT.
This article reviews the clinicopathologic features of EWS/pPNET and desmoplastic small round cell tumor in the spectrum of tumors with EWS gene rearrangements.
Diagnosis of a DSRCT was confirmed on molecular analysis with positive -RT-PCR and sequencing results for EWS-WT1 transcript and negativity for EWS-FL1.
Our detailed analyses of a novel target of EWS/WT1 in DSRCT reveal an insight into the oncogenic mechanism of EWS-fusion chromosomal translocation gene products and provide a new marker for DSRCT.
Herein, we describe a desmoplastic small round cell tumor of soft tissue with an unusual pattern of WT1 expression associated with a novel variant EWS-WT1 fusion transcript.
The current case emphasizes the utility of fluorescence in situ hybridization to demonstrate EWS-WT1 gene fusion in desmoplastic small round cell tumor with nonclassic morphologic and immunohistochemical features to avoid potential misdiagnosis.
A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene.