Abstract 5861: BOP1 expression contributes to the proliferative/invasive phenotype in melanoma

We recently performed whole exome sequencing of 30 melanocytic nevi which surprisingly revealed numerous regions of copy number loss. It was found that common reticular nevi (mostly with a junctional component) have a high incidence of copy number aberrations (CNA). Importantly, concurrent with the loss of tumor suppressor genes (e.g. CDKN2A, TP53, and NF1) was the loss of potent oncogenes (e.g. NRAS, MITF, and MDM2). We postulated that the balanced nature of these CNAs confers protection from transformation, thus keeping the lesion in the benign state. Along with copy-number loss of these well-known genes, further interrogation of these data revealed a loss on chr8q24.3 which was frequently observed in 7/30 (23%) nevi. In the smallest region of overlap, the block of proliferation 1 (BOP1) gene was identified as a candidate for functional validation. BOP1 is part of the trimeric “PeBoW” complex, essential for ribosome biogenesis and cell cycle progression. In melanoma cell lines (MM96L, HT144, and MM253), we used siRNA mediated gene targeting to achieve differing BOP1 expression levels (high, low, absent), which resulted in altered cell states. For example, high BOP1 expression caused an increase in proliferation and colony formation, whereas low BOP1 expression conferred reduced proliferation, colony formation, and a senescent like phenotype. Interestingly, low BOP1 expression also resulted in increased migration and invasive capacity. BOP1 immunofluorescence assessment of benign nevi revealed limited expression whereas in early invasive melanomas, BOP1 expression was clearly evident in proliferative melanoma nests. These data support the role of BOP1 playing a role in melanoma progression by contributing to phenotype switching. Citation Format: Mitchell S. Stark, Sabrina Hammerlindl, Lisa Tom, Kasturee Jagirdar, Jean-Marie Tan, Helmut Schaider, Richard A. Sturm, Blake O9Brien, Michael Walsh, Angus Collins, H.Peter Soyer. BOP1 expression contributes to the proliferative/invasive phenotype in melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5861.