Abstract 776: Functional analysis of BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) in melanoma.

Abstract

Abstract In the US alone, 44,250 men and 32,000 women are expected to be diagnosed with melanoma in 2012. Metastatic melanoma is the leading cause of skin cancer-related deaths worldwide. In the metastatic cutaneous melanoma (CM), anti-BRAF and anti-MEK agents have recently been shown to attenuate progression of the disease, though durable responses are still rare (NEJM articles). For metastatic ocular melanoma (OM), there is currently no established treatment strategy. Thus, one major unmet need in the field is the identification of novel “driver” physiologies which underpin the progression of disease and which can be leveraged for therapeutic gain. One new component in the ubiquitination pathway that has been recently implicated in the biology of both CM and OM is BRCA1 associated protein-1 (BAP1). Preliminary data from our laboratory showed that germline inactivating mutations of BAP1 predispose individuals to both CM and metastatic OM along with other neoplasms. In this study we examined the effects of BAP1 knockdown and overexpression on melanoma cell lines and primary melanocytes. BAP1 gene is mutated in melanoma and reported to be tumor suppressor, however suppression of BAP1 led to paradoxical growth inhibition, suggesting that the effects of BAP1 may be context dependent. Currently we are performing global gene expression and allele specific functional studies in an effort to identify novel substrates and other pathways impacted by BAP1. These findings may provide mechanistic insight into the role of BAP1 in melanoma pathogenesis. Citation Format: Raj Kumar, Ching-Ni Njauw, Zhenyu Ji, Benchun Miao, Michael Taylor, Anpuchchelvi Rajadurai, Durga Udayakumar, Hensin Tsao. Functional analysis of BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) in melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 776. doi:10.1158/1538-7445.AM2013-776