27. Genome imaging of head and neck solid tumors: Oropharyngeal, tongue, and thyroid cancers

      Large structural variants (SVs), such as insertions, deletions, and translocations are not readily detected using standard methods of whole genome analysis. Genome imaging using the Saphyr instrument from Bionano Genomics detects large (>500bp) and complex SVs that are difficult to detect using traditional short read sequencing alone. We have isolated high-molecular weight DNA (>150,000 bp) from various solid head and neck tumors using a nanobind disc, consisting of novel nano structured silica surrounding a paramagnetic disk. This DNA is bar-coded using a direct labeling enzyme at a 6 bp consensus sequence scattered throughout the human genome. Cancer genome maps are assembled de novo based on label pattern overlap and subsequently compared to a labeled human reference genome to identify SVs. We have successfully applied this framework to various head and neck solid tumors, including Human Papillomavirus (HPV)-positive oropharyngeal cancer, tongue cancer, and thyroid cancer. Genome imaging combined with whole genome sequencing can identify HPV insertion sites into the human genome of oropharyngeal cancers, and we have found viral integration to be associated with high genomic instability and more advanced clinical disease. Anaplastic thyroid cancer is a particularly aggressive form of cancer with strong genetic drivers that can be described using the genome imaging platform. Short read sequencing in the literature has been inconclusive regarding the genetic difference between young and elderly tongue cancer, but genome imaging is able to detect different SVs between the two cohorts, which may suggest distinct cancer types.
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