SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

We suggest that HGESS with BCOR alterations may warrant reclassification as 'BCOR-altered uterine sarcomas'.

In this study, EZH2 levels were modulated by CRISPR/Cas9 gene editing and PRC2 activity was inhibited with EZH2 inhibitor EPZ6438 or EED inhibitor MAK683. This was accompanied by increased expression of other PcG genes, including EZH1, CBX2, RING1, EED, and SUZ12, suggesting a compensatory interaction between PRC2 and PRC1 complexes. These findings provide significant clinical relevance, both in elucidating the mechanisms of novel molecular targets and in guiding treatment strategies for lung cancer when using epigenetic inhibitors.

P2, N=25, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Apr 2026 --> Apr 2027

Identifying effective molecular targets for treatment and enhancing sensitivity to gemcitabine (GEM) could significantly improve the management of PDAC patients...SUZ12 expression is found to be elevated in GEM-resistant (GR) PDAC cells, and decrease of SUZ12 levels increases GEM sensitivity in PDAC cells. The combination of SUZ12 knockout with GEM shows enhanced synergistic effects in cancer therapy and sensitizes GR cells to GEM, providing new insights into overcoming GEM resistance and highlighting SUZ12 as a potential target for clinical intervention in PDAC patients.

Finally, in an activating NRAS-mutant (p.Q61R) HG-ESS xenograft, the combination of MEK and FAK inhibition dramatically suppressed tumor growth and prolonged survival, highlighting a promising targeted treatment strategy. Overall, our comprehensive analysis defines the molecular basis of ESS and provides a strong preclinical rationale for precision therapies in this aggressive cancer.

Beyond their diagnostic utility, these molecular signatures increasingly inform prognosis and highlight potential therapeutic targets, including CDK4/6 inhibition, PI3K/AKT/mTOR blockade, and immunotherapy. This review summarizes the evolving molecular landscape of uterine mesenchymal tumors, underscoring the value of integrating molecular testing into clinical practice to enhance diagnostic precision and enable personalized management of these rare yet clinically significant neoplasms.

Therapeutic targeting of H3K27me3 with EZH2-selective inhibitors such as tazemetostat has shown clinical benefit in lymphoma; however, their efficacy is limited by functional redundancy with EZH1. The dual EZH1/2 inhibitor valemetostat overcomes this limitation by reactivating tumor suppressor genes, achieving durable responses in ATL and peripheral T-cell lymphoma (PTCL). Nonetheless, therapeutic resistance can emerge through PRC2 gatekeeper mutations and compensatory DNA methylation. These findings underscore the value of targeting the dysregulated epigenome and support the continued clinical development of dual EZH1/2 inhibitors.

In primary human T cells, reduced CD2 costimulation impaired the magnitude of proliferation and IFN-γ production. These findings identify BAP1 as a central regulator of receptor expression and highlight CD2 as a tunable modulator of human T cell responses.

The development of new agents for MPNST treatment has shifted away from solely targeting RAS pathway gene products to stimulating the immune system and manipulating other MPNST driver mutations such as CDKN2A/B, SUZ12, EED, and TP53. This review presents recent advances in the treatment of sarcomas and the future of drug development targeting MPNSTs.

In summary, we expand upon descriptions of H3K27me3 labeling in MCC and characterize patterns of H3K27me3 in other tumor types including small cell carcinomas and olfactory neuroblastoma. Our findings support diagnostic utility for the widely available marker H3K27me3 in MCC, with weaker labeling favoring MCC over mimics in challenging cases.

PINK1 acts as a tumor suppressor in colorectal cancer by inhibiting proliferation and migration, promoting apoptosis, and remodeling the epigenetic landscape through altering histone modifications and enhancing chromatin accessibility.

We present a novel genetically engineered mouse model that faithfully recapitulates human PRC2-loss MPNST, enabling mechanistic and preclinical studies of malignant transformation in the context of PRC2 loss.