What question did this study set out to answer?

The research aims to define how BAP1 loss alters chromatin accessibility and transcription factors in uveal melanoma.

April 5, 2026

Abstract 3198: BAP1 loss rewires chromatin and lineage identity in uveal melanoma

Key Points

The research aims to define how BAP1 loss alters chromatin accessibility and transcription factors in uveal melanoma.
Profiled epigenome using ATAC-seq, RNA-seq, and CUT&RUN for repressive histone marks.
Identified differential chromatin accessibility with DiffBind.
Performed motif enrichment analysis with HOMER.
Integrated multi-omic data with public datasets from uveal melanoma.
BAP1 loss caused a global reduction in H2AK119Ub and changes in H3K27me3 distribution.
Certain genomic regions became more accessible, linked to a neural crest-like invasive program.
AP-2 motifs enriched in accessible regions indicate a switch toward more permissive chromatin states.
The findings correlate with a loss of melanocytic identity in aggressive tumors.

Abstract

Abstract Background: BAP1 is a chromatin-associated deubiquitinase that antagonizes Polycomb Repressive Complex 1 (PRC1)-mediated ubiquitination, thereby stabilizing chromatin accessibility and genomic integrity. Uveal melanoma is the most common intraocular cancer in adults and loss of BAP1 tracks with a high-risk, metastatic phenotype. However, how BAP1 loss reprograms the epigenetic landscape to drive these lineage and phenotypic changes remains unknown. Our objective is to define the chromatin and transcriptional consequences of BAP1 loss in uveal melanoma. Description of experimental procedures: To identify regulatory mechanisms altered secondary to BAP1 loss, we profiled the epigenome upon BAP1 loss using ATAC-seq, RNA-seq, and CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3198.

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