ArticleActa neuropathologica2021
Enhancer reprogramming in PRC2-deficient malignant peripheral nerve sheath tumors induces a targetable de-differentiated state.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Induced pluripotent stem cell-derived models of malignant nerve sheath tumor progression mimic glial to neuro-mesenchymal transition and uncover therapeutic opportunities.Nature communications · 2026Article
- The Cell Surface Proteome of Malignant Peripheral Nerve Sheath Tumors Reveals Therapeutic Targets.bioRxiv : the preprint server for biology · 2026Article
- Single-cell transcriptomic profiling of malignant peripheral nerve sheath tumors.Neuro-oncology advances · 2026Review
- DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors.Scientific reports · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Schwann cells in regeneration and cancer: an epithelial-mesenchymal transition perspective.Open biology · 2025Review
- A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.Cancers · 2025Review
- [Analysis of clinical features, treatment methods, and prognostic influence factors in patients with malignant peripheral nerve sheath tumor].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2024Article
- Zebrafish-A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers.Cancers · 2024Review
- RRM2 as a novel prognostic and therapeutic target of NF1-associated MPNST.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- FOXM1 promotes neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor progression in a NUF2-dependent manner.Cancer gene therapy · 2023Article
- Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.Journal of neuro-oncology · 2023Article
- Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- CDX2 expression in malignant peripheral nerve sheath tumour: a potential diagnostic pitfall associated with PRC2 inactivation.Histopathology · 2022Article
- Loss of H3K27me3 expression in canine nerve sheath tumors.Frontiers in veterinary science · 2022Article
- High enhancer activity is an epigenetic feature of HPV negative atypical head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2022Article
- The cell surface proteome of malignant peripheral nerve sheath tumors reveals therapeutic targets.Neuro-oncology advancesArticle
- Multiomic analyses reveal new targets of polycomb repressor complex 2 in Schwann lineage cells and malignant peripheral nerve sheath tumors.Neuro-oncology advancesArticle
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Authors and funding
33 authors at 4 institutions in 1 country.
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Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that frequently harbor genetic alterations in polycomb repressor complex 2 (PRC2) components-SUZ12 and EED. Here, we show that PRC2 loss confers a dedifferentiated early neural-crest phenotype which is exclusive to PRC2-mutant MPNSTs and not a feature of neurofibromas. Neural crest phenotype in PRC2 mutant MPNSTs was validated via cross-species comparative analysis using spontaneous and transgenic MPNST models. Systematic chromatin state profiling of the MPNST cells showed extensive epigenomic reprogramming or chromatin states associated with PRC2 loss and identified gains of active enhancer states/super-enhancers on early neural crest regulators in PRC2-mutant conditions around genomic loci that harbored repressed/poised states in PRC2-WT MPNST cells. Consistently, inverse correlation between H3K27me3 loss and H3K27Ac gain was noted in MPNSTs. Epigenetic editing experiments established functional roles for enhancer gains on DLX5-a key regulator of neural crest phenotype. Consistently, blockade of enhancer activity by bromodomain inhibitors specifically suppressed this neural crest phenotype and tumor burden in PRC2-mutant PDXs. Together, these findings reveal accumulation of dedifferentiated neural crest like state in PRC2-mutant MPNSTs that can be targeted by enhancer blockade.
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