Michael Dean from the National Cancer Institute presented at the Nanopore Community Meeting in Boston on “Diverse structural variants cluster near breakage-fusion-bridge site in cancer genomes.” Dean spoke about oncogene amplification and the need for high-quality cancer genomes for SV analysis. They have developed a standard extraction method with size selection to obtain long reads. Dean uses the Severus tool for phasing and somatic SV calling, which Wakhan and the team developed. Dean applied this to cervical cancer, demonstrating how the YAP1 oncogene amplification occurs. Importantly, they found the breakage-fusion-bridge (BFB) mechanism in several cancers. Interestingly, a summer student found a non-BFB amplification in a cell line. Dean found that BFB events are significantly associated with other SVs. Another summer student in the lab characterized a cervical tumor with YAP1 BFB and HPV integration. Dean wants to go from DNA to function and learn the impact on the epigenome and gene expression. They are using the direct RNA sequencing kit to examine transcriptomes. They have learned that YAP1 expresses at least twelve isoforms with differing functions/stability. Dean’s lab is exploring the detection of open chromatin and imprinted genes. Dean concluded that “a complete understanding of structural variants is critical to cancer diagnosis and therapy” and that new tools are helping understand variation and the impact of dysregulation.
