{"entity":{"id":"paper-lee-prc2-mpnst-nat-genet-2014","kind":"paper","name":"PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumours","aka":[],"tldr":"Sequencing showed that most malignant peripheral nerve sheath tumours lose the polycomb repressive complex 2 through EED or SUZ12 mutations, on top of NF1 and CDKN2A loss, explaining their biology and giving pathologists the H3K27me3 stain that diagnoses them.","summary":"Genomic analysis of malignant peripheral nerve sheath tumours identifying loss-of-function alterations in EED or SUZ12, components of PRC2, in 70 percent of sporadic and 90 percent of radiotherapy-associated tumours, co-occurring with NF1 and CDKN2A inactivation, leading to loss of H3K27 trimethylation and amplified Ras signalling.","asOf":"2026-09-17","links":[{"label":"Nat Genet 2014","url":"https://doi.org/10.1038/ng.3095"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/25240281/"}],"tags":[],"related":[],"cancers":["malignant-peripheral-nerve-sheath-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2014,"doi":"10.1038/ng.3095","pmid":"25240281","authors":"Lee W, Teckie S, Wiesner T, et al.","paperType":"translational","findings":["PRC2 component loss (EED or SUZ12) in 70 to 90 percent of MPNST.","Complete loss of H3K27me3 in PRC2-deficient tumours."],"whatItMeans":"Loss of H3K27me3 immunostaining is now a diagnostic marker for MPNST, and PRC2 loss is a target for epigenetic and combination therapies under investigation.","caveats":["Therapeutic exploitation of PRC2 loss remains experimental."],"changedPractice":true},"route":"/key-papers/paper-lee-prc2-mpnst-nat-genet-2014/","neighbours":{"cancer":[{"id":"malignant-peripheral-nerve-sheath-tumour","kind":"cancer","name":"Malignant peripheral nerve sheath tumour (MPNST)","route":"/cancers/malignant-peripheral-nerve-sheath-tumour/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}]}}