Genomic structural variants comprise a significant fraction of somatic mutations driving
cancer onset and progression. However, such variants are not readily revealed by standard next-generation sequencing. Optical genome mapping (OGM) surpasses short-read sequencing in detecting large (>500 bp) and complex structural variants (SVs) but requires isolation of ultra-high-molecular-weight
DNA from the tissue of interest. We have successfully applied a protocol involving a paramagnetic nanobind disc to a wide range of solid
tumors. Using as little as 6.5 mg of input
tumor tissue, we show successful extraction of high-molecular-weight genomic
DNA that provides a high genomic map rate and effective coverage by optical mapping. We demonstrate the system's utility in identifying somatic SVs affecting functional and
cancer-related genes for each sample. Duplicate/triplicate analysis of select samples shows intra-sample reliability but also intra-sample heterogeneity. We also demonstrate that simply filtering SVs based on a GRCh38 human control database provides high positive and negative predictive values for true somatic variants. Our results indicate that the solid tissue
DNA extraction protocol, OGM and SV analysis can be applied to a wide variety of solid
tumors to capture SVs across the entire genome with functional importance in
cancer prognosis and treatment.