ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2017
EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 80 citations in OpenAlex.
- Genome-wide association study meta-analysis identifies susceptibility loci informing Ewing sarcoma etiology and potential mechanisms of risk.medRxiv : the preprint server for health sciences · 2026Article
- Identification of ATP9A-NFATC2 gene fusion transcript in Behcet's disease, a subtype of uveitis.Indian journal of ophthalmology · 2026Article
- Primary Ewing's Sarcoma of the Sinonasal Region: A Rare Clinical Encounter.Case reports in pathology · 2026Article
- Upregulation of POLE and proficient DNA repair are features of CIC::DUX4 sarcomas.NPJ precision oncology · 2025Article
- Confirmatory diagnosis and successive chemotherapeutic treatments of metastatic skeletalOncology letters · 2025Article
- Sarcomas with EWSR1::Non-ETS Fusion (EWSR1::NFATC2 and EWSR1::PATZ1).Surgical pathology clinics · 2024Review
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- The Recent Advances in Molecular Diagnosis of Soft Tissue Tumors.International journal of molecular sciences · 2023Review
- Top 10 Histological Mimics of Neuroendocrine Carcinoma You Should Not Miss in the Head and Neck.Head and neck pathology · 2023Review
- The ETS transcription factor ETV6 constrains the transcriptional activity of EWS-FLI to promote Ewing sarcoma.Nature cell biology · 2023Article
- Ewing and Ewing-like sarcomas: A morphological guide through genetically-defined entities.Pathology international · 2023Review
- Novel combination of imipridones and histone deacetylase inhibitors demonstrate cytotoxic effect through integrated stress response in pediatric solid tumors.American journal of cancer research · 2023Article
- Activity of pazopanib inOncoscience · 2023Article
- Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.Cell reports · 2022Article
- Does PAX7 and NKX2.2 immunoreactivity in Ewing sarcoma have prognostic significance?Virchows Archiv : an international journal of pathology · 2022Article
- The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.Frontiers in oncology · 2022Review
- Diagnosis of soft tissue tumors using immunohistochemistry as a surrogate for recurrent fusion oncoproteins.Seminars in diagnostic pathology · 2022Review
- Integrative sequencing discovers an ATF1-motif enriched molecular signature that differentiates hyalinizing clear cell carcinoma from mucoepidemoid carcinoma.Oral oncology · 2021Article
- Multiscale-omic assessment of EWSR1-NFATc2 fusion positive sarcomas identifies the mTOR pathway as a potential therapeutic target.NPJ precision oncology · 2021Article
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9 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
PAX7 is a paired-box transcription factor that is required for the developmental specification of adult skeletal muscle progenitors in mice. We previously demonstrated PAX7 expression as a marker of skeletal muscle differentiation in rhabdomyosarcoma. Here, using analyses of published whole-genome gene expression microarray data, we identify PAX7 as a gene with significantly increased expression in Ewing sarcoma in comparison to CIC-DUX4 round cell sarcoma. Analysis of PAX7 in a large cohort of 103 Ewing sarcoma cases by immunohistochemistry revealed expression in 99.0% of cases (102/103). PAX7 expression was noted in cases demonstrating three distinct Ewing sarcoma EWSR1 translocations involving FLI1, ERG, and NFATc2. No PAX7 expression was observed in any of 27 cases of CIC-DUX4 sarcoma by immunohistochemistry (0%; 0/27). Exploring the mechanism of PAX7 expression in Ewing sarcoma using curated RNA- and ChIP-sequencing data, we demonstrate that the EWSR1 fusion protein is required for PAX7 expression in Ewing sarcoma and identify a candidate EWSR1-FLI1-bound PAX7 enhancer that coincides with both a consensus GGAA repeat-containing binding site and a peak of regulatory H3K27 acetylation. Taken together, our findings provide mechanistic support for the utility of PAX7 immunohistochemistry in the diagnosis of Ewing sarcoma, while linking this sarcoma of uncertain histogenesis to a key transcriptional regulator of mammalian muscle progenitor cells.
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