Nat CommunJClub
Synthetic lethal screens reveal p300/CBP as a vulnerability for GNAQ-driven uveal melanomas.
Nature Communications · · Journal Article · Open access
Zhang, Yuan + more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
p300 (EP300) is a top synthetic lethal vulnerability in GNAQ-mutant uveal melanoma, with CREBBP (CBP) also ranking among the strongest hits.
- Why it matters: Limited treatments exist for uveal melanoma, especially metastatic disease, and GNAQ-driven tumors need actionable, mutation-linked vulnerabilities.
- What they did: Using an isogenic CRISPR screening strategy, the study tested GNAQ-mutant contexts and then mapped p300/CBP roles in YAP-dependent transcription via chromatin interactions, H3K27 acetylation, and RNA polymerase II/CDK9 recruitment.
- The result: In multiple in vivo models spanning clinically relevant GNAQ-mutant stages, p300 inhibition—genetic and pharmacological—profoundly impairs tumor growth and metastasis, supporting p300 as a therapeutic target tied to unrestrained YAP signaling.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.
- Open access