BRCA1-Associated Protein 1 in Sarcoma

Soft tissue sarcomas (STSs) are genetically complex mesenchymal tumors with limited therapeutic options. BRCA1-associated protein 1 (BAP1), a deubiquitinase, is a critical regulator of chromatin architecture, DNA repair, and cell cycle control. While BAP1 alterations are well-characterized in mesothelioma and uveal melanoma, their role in STS remains understudied. Increasing evidence shows BAP1 alterations are associated with STS. This review summarizes current evidence on BAP1 biology and its emerging significance in sarcoma. We discuss BAP1’s molecular functions, including its role in the Polycomb Repressive Deubiquitinase (PR-DUB) complex, and summarize recent findings implicating BAP1 loss in multiple subtypes of STS. We highlight mechanistic links between BAP1 deficiency, genomic instability, and tumor progression, and explore therapeutic implications such as polo-like kinase 1 (PLK1) inhibition and epigenetic modulation. Understanding BAP1-driven pathways in STS may uncover novel biomarkers and targeted strategies, addressing a critical unmet need in sarcoma management.