Michael Dean from the National Cancer Institute spoke at London Calling 2022 about “Understanding cancer epigenetics, immunogenetics, and energetics.” Dean explained why they hate cancer and its impact on their family. Dean said that “cancer is more like a puzzle that has to be solved before you can have a rational solution.” The current analogy Dean uses is “the cancer moonshot.” They noted that the causes of cancer are mostly known. Dean talked about the discovery of pathways critical for development are also important for cancer, and ” cancer is caused by chronic tissue damage and inflammation.” Dean described a cervical cancer study in Guatemala and how Human Papilloma Virus (HPV) contributes to this disease. HPV integrates and has complex integration sites. Dean explained that they used direct cDNA sequencing to better understand expression of HPV. THey have learned that the virus seems to regulate the epigenome to turn on and off oncogenes. They directly identified methylation and confirmed with bisulfite sequencing. Dean’s team then used direct RNA sequencing to identify RNA modifications. The team studied the PI3K inhibitor and also the 3D DNA structure using the Pore-C crosslinking method. Dean summarized that they have used Nanopore sequencing to identify mechanisms of HPV cell transformation. Dean ended with a challenge: can we determine low cost, point-of-care HPV diagnostics? Dean and team used a variety of approaches including cDNA and direct RNA sequencing as well as Pore-C to better understand cancer epigenomics. This session also included snippets of history and personal connections to cancer.
