MD - Penn State Health / Otolaryngology - Head and Neck Surgery Resident
BIOGRAPHY
JUN 12, 2020 8:00 AM PDT
Genome imaging of head and neck solid tumors: oropharyngeal, tongue, and thyroid cancers
Speaker
Event Date & Time
DATE: June 12, 2020
TIME: 8:00 am PDT, 11:00 am EDT
Abstract
Whole genome imaging using the Saphyr instrument from Bionano detects structural variants (SVs), such as insertions, deletions, and translocations, not readily evident from standard methods of whole genome analysis. This technology is particularly useful for detecting 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 protocol using a nanobind disc, consisting of novel nano structured silica surrounding a thermoplastic 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 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 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 in cell cycle regulation 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 affecting Ras signaling and the cell cycle between the two cohorts.
Learning Objectives:
- Understand the solid tumor high-molecular weight DNA isolation process
- Review whole genome imaging findings of head and neck cancers
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