| http://purl.uniprot.org/citations/31023785 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31023785 | http://www.w3.org/2000/01/rdf-schema#comment | "Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas typically developing in the context of neurofibromatosis type 1 (NF-1). With the exception of surgical resection, these tumors are resistant to all current therapies, and unresectable, recurrent, or metastatic tumors are considered incurable. Preclinical studies have identified several novel candidate molecular targets for therapeutic intervention, but, to date, targeted therapies have proven ineffective. Recent studies have identified recurrent mutations in polycomb repressive complex 2 (PRC2) core components, embryonic ectoderm development protein (EED) and suppressor of zeste 12 homolog (SUZ12), in MPNST. These mutations result in global loss of the histone H3 lysine 27 trimethylation epigenetic mark, normally deposited by PRC2, and subsequent gain in acetylation at this residue. This altered chromatin state has been shown to promote MPNST malignancy; however, acetylation at this residue sensitizes MPNSTs to BRD4 and bromodomain and extra-terminal domain inhibition. Interestingly, the catalytic component of PRC2, enhancer of zeste homolog 2 (EZH2), is not mutated in MPNST, hinting that a noncanonical, PRC2-independent function of EZH2 may play a role in this cancer. This review examines the pathobiology of MPNST, the contribution of PRC2 subunits to this process, and the prospects for PRC2-related therapies for this cancer. IMPLICATIONS: Identification of mutations in the PRC2 components EED and SUZ12 in the majority of MPNSTs may imply noncanonical oncogenic activities of the intact component, EZH2, and provide new opportunities for therapeutic intervention."xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.org/dc/terms/identifier | "doi:10.1158/1541-7786.mcr-19-0147"xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/author | "Lombard D.B."xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/author | "Korfhage J."xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/name | "Mol Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/pages | "1417-1428"xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/title | "Malignant Peripheral Nerve Sheath Tumors: From Epigenome to Bedside."xsd:string |
| http://purl.uniprot.org/citations/31023785 | http://purl.uniprot.org/core/volume | "17"xsd:string |
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