Objective: To detect the EWS-WT1 chimeric mRNA in desmoplastic small round cell tumor (DSRCT) and its clinicopathological significance.
Methods: Formalin fixed, paraffin-embedded tumor specimens from 4 examples of this entity were studied by reverse transcriptase polymerase chain reaction to detect the EWS-WT1 fusion transcripts resulting from the chromosomal translocation t(11;22)(p13;q12). The following tumor specimens were included as controls: 2 Ewing's sarcomas/primitive neuroectodermal tumors (PNET/ES), 2 alveolar rhabdomyosarcomas, and 2 lymphomas.
Results: EWS-WT1 fusion transcripts were detected in 3 of 4 desmoplastic small round cell tumors but not in any other tumor types studied as controls.
Conclusion: The analysis of the EWS-WT1 fusion transcript which was performed on formalin-fixed, paraffin-embedded tissues is a sensitive and specific method in the diagnosis and differential diagnosis of DSRCT.
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Cancer Res
January 2025
The ATIP-Avenir Inserm and ERC StG (Epi)genetic Vulnerabilities in Solid Tumors and Sarcoma Laboratory, Inserm Unit UMR 981, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
Nat Commun
August 2024
Experimental Pathology Service, Lausanne University Hospital & University of Lausanne, Lausanne, Switzerland.
EWS fusion oncoproteins underlie several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive cancer driven by EWS-WT1 fusion proteins. Here we combine chromatin occupancy and 3D profiles to identify EWS-WT1-dependent gene regulation networks and target genes. We show that EWS-WT1 is a powerful chromatin activator controlling an oncogenic gene expression program that characterizes primary tumors.
View Article and Find Full Text PDFCancers (Basel)
March 2023
Center for Immuno-Oncology, Department of Radiation Oncology, Taussig Cancer Institute and Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
(1) Background: EWS fusion genes are associated with Ewing sarcoma and other Ewing family tumors including desmoplastic small round tumor, DSRCT. We utilize a clinical genomics workflow to reveal real-world frequencies of EWS fusion events, cataloging events that are similar, or divergent at the EWS breakpoint. (2) Methods: EWS fusion events from our next-generation sequencing panel (NGS) samples were first sorted by breakpoint or fusion junctions to map out the frequency of breakpoints.
View Article and Find Full Text PDFMol Cancer Ther
August 2022
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Desmoplastic small round cell tumor (DSRCT) is a rare pediatric sarcoma with poor overall survival. This tumor is absolutely dependent on the continued expression and activity of its defining molecular lesion, the EWS-WT1 transcription factor. Unfortunately, the therapeutic targeting of transcription factors is challenging, and there is a critical need to identify compounds that inhibit EWS-WT1.
View Article and Find Full Text PDFFront Oncol
September 2021
Department of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.
Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare and highly malignant soft tissue neoplasm, which is characterized by rapid progression and poor prognosis. The mechanism underlying the development of this neoplasm remains elusive, but all cases are characterized by the chromosomal translocation t (11;22) (p13; q12), which results in a formation of EWSR1-WT1 gene fusion. The diagnosis of IDSRCT is often made with core-needle tissue biopsy specimens or laparoscopy or laparotomy.
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