BRCA1 Associated Protein 1 (BAP1) is a tumor suppressor gene with identified mutations in various cancers including uveal melanoma (UM), malignant mesothelioma, renal cell carcinoma, and cutaneous melanoma. The protein forms multicomplexes with various transcription factors and cell cycle regulators. It also functions as a deubiquitylating enzyme primarily located in the nucleus and acts on histone 2A, leading to altered gene transcription. Recently, it was shown to play a role in apoptotic signaling, homologous-directed repair, and ferroptosis regulation. Over 90% of metastatic UM cases report loss-of-function BAP1 mutations. There is a strong association between loss-of-function BAP1 mutations, metastasis, and poor disease prognosis, the mechanisms for which remain unclear. Understanding the role of BAP1 in metastasis may help uncover therapeutic approaches and improve overall survival outcomes for metastatic UM patients. Here we used a multi-omics approach to investigate changes in gene expression in UM with BAP1 loss. Bioinformatics analysis using multiple UM patient and cell line data sets revealed upregulation of key cell-cell adhesion genes, CDH1, CADM1, and SDC2 with loss of BAP1. These adhesion proteins may be involved with facilitating collective migration or enable metastatic seeding. Together, these data prompt further investigation into the specific roles of BAP1 during the metastatic cascade in UM, from primary dissemination in the eye to seeding in the liver.

Citation Format: Usman Baqai, Timothy Purwin, Nelisa Bechtel, Vivian Chua, Anna Han, Andrew E. Aplin. Multiomics profiling of BAP1 loss in uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 167.