EWSR1 (EWS RNA Binding Protein 1)

This case highlights the relevance of EWSR1-driven fusions in spindle cell mesenchymal neoplasms and emphasizes the need for further exploration into their clinical and biological behavior. After 5 months of chemotherapy, the patient showed moderate clinical improvement.

Molecular genetic studies identified a novel EWSR1::TEAD3 gene fusion. This is the first reported case of a peritoneal mesothelioma harboring this fusion.

P2/3, N=437, Active, not recruiting, Children's Oncology Group | Trial completion date: Jul 2032 --> Dec 2027 | Trial primary completion date: Jul 2032 --> Dec 2027

By examining ETS family-related fusions in all samples, known fusions were validated, and rare breakpoint variants, including novel ones within the intronic region between EWSR1 exon 11 and FLI1 exon 6, were discovered. The novel assembly-based approach for fusion gene detection improves accuracy in short-read sequencing data, offers a customizable research platform, and shows promise for future applications with long-read sequencing technologies.

Consistent with the longer doubling time, PDES were more resistant to doxorubicin, etoposide and vincristine and ionising radiation (p < 0.0001) than cell lines. PDES were sensitive to mTKIs (cabozantinib, lenvatinib, and regorafenib), and trabectedin. The response of PDES to drugs in vitro reflects the clinical experience of patients. Models incorporating PDES cells may positively contribute to the preclinical pipeline.

This case highlights the diagnostic difficulty and rapid progression of renal Ewing sarcoma. Accurate diagnosis relies on integrated imaging, histopathology, immunoprofiling, and molecular testing. Early recognition and multidisciplinary decision-making are essential for optimizing outcomes in this rare tumor entity.

PPMS is an extremely rare low-grade sarcoma with significant diagnostic implications due to its genetic characteristics. Surgical resection remains the primary treatment modality, though the potential for local recurrence or metastasis necessitates ongoing monitoring and further research to establish standardized treatment protocols and understand its biological behavior.

Herein, we present a case of intracranial CIC::DUX4 rearrangement diagnosed using DNA methylation classifiers and multiple omics diagnosis techniques. We also document the disease progression after chemoradiation therapy and subsequent in situ recurrence.

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Dec 2025 --> Dec 2026

We found that LY2835219 and trabectedin significantly alter the nuclear distribution of endogenous EWS::FLI1, disrupting and mislocalizing EWS::FLI1 hubs, respectively. Together, our results reveal new insights into the assembly and regulation of endogenous EWS::FLI1 hubs at an unprecedented resolution. The methodology developed here will be useful for characterizing the functional hubs of many regular and pathological TFs in the future.

Histopathology revealed a highly cellular neoplasm of uniform small round blue cells arranged in sheets and nests, immunoreactive for cluster of differentiation 99 (CD99) with diffuse membranous staining and negative for AE1/AE3, desmin, CD45, and S100. Targeted next-generation sequencing confirmed an EWSR1/FLI1 fusion, establishing the diagnosis of ES.

The MRI triad of fusiform enlargement, T2 hyperintensity and homogeneous enhancement strongly supports INP diagnosis and may obviate biopsy in typical cases. Our hotspot-limited assay detected TRAF7 mutations in only 22.2%, underscoring methodological limitations and probable genetic heterogeneity. Despite an indolent imaging appearance, INP frequently causes severe functional impairment requiring reconstructive surgery. Early recognition, structured functional monitoring and risk-adapted intervention are essential to optimise outcomes.