Dataset Information

Desmoplastic Small Round Cell Tumor of the Uterus: A Report of Molecularly Confirmed Case with EWSR1-WT1 Fusion.

ABSTRACT: We report a case of a 49-year-old female with desmoplastic small round cell tumor of the uterus (DSRCT). Histologically, in some areas the tumor showed typical features with ample desmoplastic stroma, while in other areas the tumor cells diffusely infiltrated myometrium with only focal desmoplastic reaction. Immunohistochemically, the tumor cells showed diffuse positivity for desmin, CD56, CD57, EMA and cyclin D1. Focal positivity was present for antibodies against cytokeratin AE1/3, BerEP4, NSE, IFITM1 and CD10. The WT-1 antibody (against the N-terminus) showed cytoplasmic positivity in some tumor cells, while the nuclei were negative. P53 expression was wild-type. The Ki-67 index (MIB1 antibody) was about 55%. Other markers examined including transgelin, myogenin, synaptophysin, chromogranin, h-caldesmon, PAX8, and CD117 were all negative. NGS analysis revealed a fusion transcript of the EWSR1 and WT1 genes. DSRCT of the uterus is a rare neoplasm, as only two cases have been reported so far. However, only one of these cases was examined molecularly with a confirmation of the characteristic EWSR1-WT1 fusion. We report a second case of molecularly confirmed DSRCT of the uterus and discuss its clinical features, differential diagnosis and the significance of molecular testing.

SUBMITTER: Dundr P

PROVIDER: S-EPMC9140206 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Desmoplastic Small Round Cell Tumor of the Uterus: A Report of Molecularly Confirmed Case with EWSR1-WT1 Fusion.

Dundr Pavel P Drozenová Jana J Matěj Radoslav R Bártů Michaela M Němejcová Kristýna K Robová Helena H Rob Lukáš L Hojný Jan J Stružinská Ivana I

Diagnostics (Basel, Switzerland) 20220510 5

We report a case of a 49-year-old female with desmoplastic small round cell tumor of the uterus (DSRCT). Histologically, in some areas the tumor showed typical features with ample desmoplastic stroma, while in other areas the tumor cells diffusely infiltrated myometrium with only focal desmoplastic reaction. Immunohistochemically, the tumor cells showed diffuse positivity for desmin, CD56, CD57, EMA and cyclin D1. Focal positivity was present for antibodies against cytokeratin AE1/3, BerEP4, NSE ...[more]

PMID: 35626339

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Project description:Desmoplastic small round cell tumor (DSRCT) is a highly aggressive cancer predominantly occurring in young male adolescents. It mainly arises at sites lined by mesothelium, such as the abdominal cavity, and is driven by the pathognomonic EWSR1::WT1 fusion oncoprotein. The dismal survival rates (5–20%) have not significantly improved since its first description in 1989, also due to a lack of comprehensive datasets that could shed new light on the biology of the disease and uncover novel diagnostic markers and therapeutic targets. Thus, we established genome-wide single-cell RNA-sequencing and bulk proteomic data of in vitro and in vivo-generated EWSR1::WT1 knockdown models and combined them with an original systems-biology-based pipeline including patient data, resulting in a rich resource for discovery analyses. This approach revealed the alpha-2/delta subunit of the voltage-dependent calcium channel complex, CACNA2D2, as a strongly overexpressed direct target of EWSR1::WT1 in DSRCTs, which is regulated by an EWSR1::WT1-bound super-enhancer. Ectopic expression of the main EWSR1::WT1 isoforms in mesothelial cells, the putative cell of origin of DSRCTs, confirmed that EWSR1::WT1 is sufficient to induce super-enhancer formation at the CACNA2D2 locus followed by robust transcription of this gene. Moreover, single-cell and bulk-level analyses on patient samples and cell line-derived xenografts highlighted CACNA2D2 as a critical mediator of the EWSR1::WT1 oncogenic signature. Based on bulk and single-cell transcriptomic data, the computed CACNA2D2 signature could be further utilized to robustly identify DSRCTs in reference sets. Finally, we show that CACNA2D2 is a highly sensitive and specific single biomarker for fast, simple, and cost-efficient diagnosis of DSRCT. Collectively, we established a freely available large-scale multi-omics dataset for this devastating disease and provide a blueprint of how such data can be used to identify a new and clinically relevant diagnostic marker, which may significantly reduce misdiagnoses, and thus improve patient care.

Dataset Information

Desmoplastic Small Round Cell Tumor of the Uterus: A Report of Molecularly Confirmed Case with EWSR1-WT1 Fusion.

Publications

Desmoplastic Small Round Cell Tumor of the Uterus: A Report of Molecularly Confirmed Case with EWSR1-WT1 Fusion.

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