EED

Overview

EED (Embryonic Ectoderm Development) encodes a core structural component of the Polycomb Repressive Complex 2 (PRC2), which catalyzes H3K27 trimethylation to silence developmental genes. In malignant peripheral nerve sheath tumors (MPNSTs), EED is frequently inactivated via loss-of-function mutations, establishing PRC2 as a tumor suppressor in this sarcoma subtype.

Alterations observed in the corpus

  • Loss-of-function mutations (4 frameshift, 1 splice-site) with LOH (heterozygous deletion or copy-neutral LOH) in MPNST discovery cohort; mutually exclusive with SUZ12 alterations PMID:25240281.
  • EED and SUZ12 alterations collectively inactivate PRC2 in 92% of sporadic, 70% of NF1-associated, and 90% of radiotherapy-associated MPNSTs PMID:25240281.

Cancer types (linked)

  • MPNST: highly recurrent loss-of-function alterations (80% of discovery cohort, up to 92% in sporadic cases); H3K27me3 loss by IHC tracks PRC2 functional status and distinguishes MPNST from benign neurofibromas PMID:25240281.

Co-occurrence and mutual exclusivity

  • Mutually exclusive with SUZ12 alterations within the same tumor PMID:25240281.
  • Significantly co-occurs with NF1 and CDKN2A alterations (Fleiss’ kappa=0.21, p=0.001) PMID:25240281.

Therapeutic relevance

  • Because PRC2 (EED/SUZ12) acts as a tumor suppressor in MPNST (contrast with EZH2 oncogenic gain-of-function in lymphoma), broad PRC2 inhibitors are unlikely to benefit; downstream PRC2-repressed pathways may be therapeutically targetable PMID:25240281.

Open questions

  • Whether EED-deficient MPNSTs respond equivalently to SUZ12-deficient tumors in functional rescue experiments remains untested PMID:25240281.

Sources

This page was processed by entity-page-writer on 2026-05-11.