My Linh Thibodeau from the University of British Columbia in Canada presented at London Calling 2019 on “Resolution of germline hereditary cancer structural variants using nanopore sequencing.” They began talking about the Personalized OncoGenomics Program (POG), which is an initiative of BC Cancer. The study enrolls participants and conducts extensive genomic analyses. The team evaluated 570 adult cases and identified 70 pathogenic variants. Eleven structural variants were selected for MinION technical validation. The examples they selected were from patients who had challenging cases and variants. Thibodeau focused on four patients. For one patient, they did four flow cells of sequencing, for example. For one patient, there was an ATM deletion. Long-range PCR results supported the ONT sequencing results. Another patient had three variants of interest. Nanopore sequencing helped identify inversions and deletions. With help from Martin Krzywinski, the creator of Circos plots, they developed a shoelace plot to visualize the mutations and breakpoints. Nanopore sequencing changed the interpretation of the next patient by identifying an insertion. The long-read sequencing results and shoelace schematics helped identify breakpoints, duplications, and deletions for the next patient. Thibodeau hopes that nanopore sequencing may become the method of choice to validate breakpoints and structural variants. The team planned to use PromethION flow cells next and expand the clinical samples for analysis. This is not the first BC Cancer study I have learned about. Structural variants are now being identified and better-understood thanks to long-read sequencing.
