The prevalence of thyroid nodules (TNs) increases linearly with age¹ and has been found to be as high as 67%.² Most TNs are benign, with only approximately 1 in 20 clinically identified nodules proving to be malignant.³ Although the likelihood of a given TN to be malignant is low, the incidence of thyroid cancer has been steadily rising in recent years, with annual increases of 5.3% and 4.5% for men and women, respectively.⁴ In 2015, there will be an estimated 62 450 new cases of thyroid cancer with an associated 1950 related deaths.⁴

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.