SUZ12
Overview
SUZ12 encodes a core component of the Polycomb Repressive Complex 2 (PRC2), which catalyzes histone H3 lysine 27 trimethylation (H3K27me3) to mediate transcriptional silencing. Loss-of-function SUZ12 alterations lead to PRC2 inactivation and are recurrent in malignant peripheral nerve sheath tumors (MPNST), where they are associated with epigenetic dysregulation.
Alterations observed in the corpus
- Inactivating mutations and deletions in 33% of RT-MPNST vs 17% of sporadic MPNST, indicating enrichment in radiation-associated MPNST PMID:37350195.
- SUZ12 undergoes homozygous and heterozygous deletions plus local genomic rearrangements producing aberrant transcripts in MPNST; mutually exclusive with EED loss; SUZ12 re-expression rescues H3K27me3 and inhibits growth PMID:25240281
Cancer types (linked)
- MPNST – SUZ12 inactivation enriched in RT-MPNST (33%) compared to sporadic MPNST (17%); PRC2 complex component PMID:37350195.
Co-occurrence and mutual exclusivity
- SUZ12 inactivation in MPNST co-occurs with NF1 inactivation (67% in RT-MPNST) and CDKN2A/CDKN2B deletions (92% in RT-MPNST) PMID:37350195.
Therapeutic relevance
- Investigations on small molecular inhibitors of DNA methyltransferase (DNMT1) are ongoing in sporadic/NF1-related and RT-MPNSTs harboring PRC2-inactivating mutations such as SUZ12 loss PMID:37350195.
Open questions
- Whether DNMT1 inhibitor efficacy differs between RT-MPNST and sporadic MPNST with PRC2 inactivation is not yet established PMID:37350195.
Sources
This page was processed by crosslinker on 2026-05-04. - PMID:25240281
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