Abstract 04: Caspase-8 is a novel candidate driver gene in head and neck squamous cell carcinoma

Abstract

Abstract Integrated genomic analysis of head and neck squamous cell carcinoma (HNSCC) has identified a heterogeneous spectrum of alterations dominated by tumor suppressor genes. An interesting new candidate driver gene is Caspase-8 (CASP8), which is mutated in 18% of oral cavity HPV-negative tumors. CASP8 is not obviously a part of any well-characterized driver pathway in HNSCC, and its role in this tumor type is unknown. In TCGA genomic data CAPS8 mutant tumors have a unique spectrum of alterations and expression changes, including a dramatic increase in markers of inflammation, which suggest they are a genomic subtype of HNSCC. CAPS8 is a key component of the extrinsic apoptotic pathway, but it also has a role in necrotic death, inflammation, and other pathways. We have characterized human and mouse CASP8 knock-out cell lines in vitro and in vivo in order to begin to understand the function of this gene in HNSCC. Loss of CASP8 function prevents extrinsic apoptosis and alters proliferation and tumorigenicity. It may also regulate the antitumor immune response. CASP8 is an exciting new candidate driver gene in HNSCC that may offer new opportunities for therapeutic intervention. Citation Format: Burak Uzunparmak, Antje Lindemann, Mitchell J. Frederick, Jeffrey N. Myers, Curtis R. Pickering. Caspase-8 is a novel candidate driver gene in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 04.