A novel bead-capture nanopore sequencing method for large structural rearrangement detection in cancer | Fisher CL, et al | Journal of Molecular Diagnostics | Dec. 2022

Abstract

Rapid, cost-effective genomic stratification of structural rearrangements in cancer is often of vital importance when determining treatment; existing diagnostic cytogenetic and molecular testing fails to deliver the required speed when deployed at scale, however. Next-generation sequencing–based methods are widely used, but these can lack sensitivity and require batching of samples to be cost-effective, with long turnaround times. Here we present a novel method for rearrangement detection from genomic DNA based on third-generation long-read sequencing that overcomes these time and cost issues. The utility of this approach for the genomic stratification of patients with acute myeloid leukemia is shown based on detection of four of the most prevalent structural rearrangements. The method not only determines the precise genomic breakpoint for each expected rearrangement but also discovers and validates novel translocations in one-third of the tested samples, 80% of which involve known oncogenes. We anticipate this method will prove to be a powerful tool for the diagnosis, genomic stratification, and characterization of cancers.