ArticleNature genetics2014
PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06114004 (Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas), which is not on this map. Cited by 373 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas
Who cites it
373 citing papers in PubMed, 2 syntheses or guidelines pooled it, 625 citations in OpenAlex.
- Survival outcomes of malignant peripheral nerve sheath tumors (MPNSTs) with and without neurofibromatosis type I (NF1): a meta-analysis.World journal of surgical oncology · 2024Pooled it
- Epidemiology, Characteristic, and Prognostic Factors of Primary Sporadic Intradural Malignant Peripheral Nerve Sheath Tumor in the Spinal Canal: A Systematic Literature Review.Frontiers in oncology · 2022Pooled it
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- Review
- Review
- TNG961 Is a Selective Oral HBS1L Molecular Glue Degrader for the Treatment of FOCAD-Deleted Cancers.Cancer discovery · 2026Article
- Establishment of a patient-derived malignant peripheral nerve sheath tumor organoid model reveals SHH pathway activation and therapeutic vulnerability.Human cell · 2026Article
- Neurofibromatosis type 1-associated gastric gastrointestinal stromal tumor with PRC2 loss.Clinical journal of gastroenterology · 2026Article
- DNA Hypomethylation Is Not Cell Intrinsically Toxic to Polycomb Repressive Complex 2 Deficient Malignant Peripheral Nerve Sheath Tumors.Genes, chromosomes & cancer · 2026Article
- Diagnosing metastatic angiosarcoma arising from MPNST using H3K27me3 staining in NF1: illustrative case.Journal of neurosurgery. Case lessons · 2026Article
- Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma.Nature communications · 2026Article
- Development of a Cre-Inducible Rabl6a Transgenic Mouse Model That Enhances Sarcoma Growth In Vivo.Cancers · 2026Article
- Circulating Tumor DNA in Neurofibromatosis Type 1: Translating Molecular Discovery into Clinical Surveillance.Diagnostics (Basel, Switzerland) · 2026Review
- 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 conserved N-terminal SANT1-binding domain (SBD) of EZH2 regulates PRC2 activity.Genes & development · 2026Article
- Immune landscape characterization of neurofibromas with atypical features in Neurofibromatosis1 reveals PD-1 and the Tim-3/Galectin-9 pathway as potential therapeutic targets.Acta neuropathologica communications · 2026Article
- A new hope: Clinical advances in targeted therapies for pediatric diffuse midline glioma.Neuro-oncology advances · 2026Review
- Diagnoses of double heterozygous NF1 variants and dual RASopathy.Molecular and cellular pediatrics · 2026Review
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- The Cell Surface Proteome of Malignant Peripheral Nerve Sheath Tumors Reveals Therapeutic Targets.bioRxiv : the preprint server for biology · 2026Article
313 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 1 country.
Funding
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) represent a group of highly aggressive soft-tissue sarcomas that may occur sporadically, in association with neurofibromatosis type I (NF1 associated) or after radiotherapy. Using comprehensive genomic approaches, we identified loss-of-function somatic alterations of the Polycomb repressive complex 2 (PRC2) components (EED or SUZ12) in 92% of sporadic, 70% of NF1-associated and 90% of radiotherapy-associated MPNSTs. MPNSTs with PRC2 loss showed complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3) and aberrant transcriptional activation of multiple PRC2-repressed homeobox master regulators and their regulated developmental pathways. Introduction of the lost PRC2 component in a PRC2-deficient MPNST cell line restored H3K27me3 levels and decreased cell growth. Additionally, we identified frequent somatic alterations of CDKN2A (81% of all MPNSTs) and NF1 (72% of non-NF1-associated MPNSTs), both of which significantly co-occur with PRC2 alterations. The highly recurrent and specific inactivation of PRC2 components, NF1 and CDKN2A highlights their critical and potentially cooperative roles in MPNST pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.