Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients

Genome Med. 2021 May 18;13(1):86. doi: 10.1186/s13073-021-00899-7.

Abstract

Here, we describe a novel approach for rapid discovery of a set of tumor-specific genomic structural variants (SVs), based on a combination of low coverage cancer genome sequencing using Oxford Nanopore with an SV calling and filtering pipeline. We applied the method to tumor samples of high-grade ovarian and prostate cancer patients and validated on average ten somatic SVs per patient with breakpoint-spanning PCR mini-amplicons. These SVs could be quantified in ctDNA samples of patients with metastatic prostate cancer using a digital PCR assay. The results suggest that SV dynamics correlate with and may improve existing treatment-response biomarkers such as PSA. https://github.com/UMCUGenetics/SHARC .

Keywords: Cancer; Genomics; Liquid biopsies; Nanopore; Structural variation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Circulating Tumor DNA*
  • Computational Biology / methods
  • Female
  • Genomic Structural Variation*
  • Humans
  • Liquid Biopsy / methods
  • Male
  • Molecular Diagnostic Techniques* / methods
  • Molecular Diagnostic Techniques* / standards
  • Nanopore Sequencing*
  • Neoplasms / diagnosis*
  • Neoplasms / genetics*
  • Organ Specificity / genetics
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA