Bromodomains in HPV Head and Neck Cancer - Using NGS to Help Understand the Transcriptional Landscape

Human papillomavirus (HPV), an 8-kb double stranded DNA virus, infects the mouth and throat and is classified as cancer of the head and neck. Amongst various HPV serotypes, HPV16 has been classified as oncogenic for a various number of cancer sites including head and neck squamous cell carcinoma (HNSCC). Integration of HPV into host genomes is not part of its life cycle. However, the exception is HNSCC wherein E6 and E7 viral proteins predominantly drive its tumor progression. This integration event is a cul-de-sac since it cannot be packaged and transmitted to neighboring cells.

To address oncogenic progression post viral integration, a family of bromodomain and extraterminal domain (BET) proteins that mediates transcription through binding to acetylated histones to recruit chromatin complexes will be investigated. Specifically, the lack of understanding of the distinct roles of BRD2 and BRD4 in regulating viral-host transcription machinery and how it impacts intrinsic mechanisms of impaired DNA repair, cell cycle control and oncogenic signaling pathways. Using a combination of NGS and biochemistry, we will determine the specificity of BRD driven transcription in HPV HNSCC cancer, and discuss transcriptional networks of integrated HPV HNSCC cells and its impact on proliferation.

Learning Objectives:

1. Explore the role of HPV in head and neck squamous cell carcinoma.

2. Explain how HPV transcription impacts cancer proliferation.

3. Discuss how Tecan’s MagicPrep NGS system simplifies library preparation.