PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumours
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.
Overview
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.
- PRC2 component loss (EED or SUZ12) in 70 to 90 percent of MPNST.
- Complete loss of H3K27me3 in PRC2-deficient tumours.
Loss of H3K27me3 immunostaining is now a diagnostic marker for MPNST, and PRC2 loss is a target for epigenetic and combination therapies under investigation.
- Therapeutic exploitation of PRC2 loss remains experimental.