# PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumours

Source: https://onco.cc/key-papers/paper-lee-prc2-mpnst-nat-genet-2014/  
OnCo record `paper-lee-prc2-mpnst-nat-genet-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Nature Genetics
- Year: 2014
- DOI: 10.1038/ng.3095
- Authors: Lee W, Teckie S, Wiesner T, et al.
- Findings: PRC2 component loss (EED or SUZ12) in 70 to 90 percent of MPNST.; Complete loss of H3K27me3 in PRC2-deficient tumours.
- What it means: 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.

## Sources

- Nat Genet 2014: https://doi.org/10.1038/ng.3095
- PubMed: https://pubmed.ncbi.nlm.nih.gov/25240281/

## Connected records

- cancers: [Malignant peripheral nerve sheath tumour (MPNST)](https://onco.cc/cancers/malignant-peripheral-nerve-sheath-tumour/)
- journals: [Nature Genetics](https://onco.cc/journals/nature-genetics/)

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