Abstract B33: Integration of genome-wide datasets identifies SOX10 as a lineage-specific genetic dependency in melanoma

Abstract

Abstract Melanoma accounts for less than 5% of skin cancers, but a majority of skin cancer deaths. Genomic studies have firmly established the role of recurrent somatic alterations in the pathogenesis of melanoma, including mutations in BRAF, NRAS, TP53, PTEN, and CDKN2A. While the discovery of activating mutations in BRAF in over 60% of melanomas has led to the development of FDA-approved BRAF and MEK inhibitors that induce dramatic responses in BRAF V600-mutant melanomas, the inevitable resistance to BRAF/MEK inhibitors necessitates a greater understanding of melanoma biology and genetics. By integrating genome-wide functional genomic and expression data, we have identified SOX10 as a lineage-specific genetic dependency in melanoma. SOX10 dependency is highly correlated with SOX10 gene expression in melanoma. Subsequent functional in vitro experiments have confirmed the role of SOX10 in the cellular proliferation and growth of melanoma cell lines. The combination of SOX10 depletion with current FDA-approved targeted therapies for melanoma hold promise for the delay or prevention of resistance to these therapeutics and may lead to more durable control of melanoma in human patients. Citation Format: Terence C. Wong, Cory M. Johannessen, Levi A. Garraway. Integration of genome-wide datasets identifies SOX10 as a lineage-specific genetic dependency in melanoma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B33.