Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients.
Jose Espejo Valle-InclanChristina StanglAnouk C de JongLisanne F van DesselMarkus J van RoosmalenJean C A HelmijrIvo RenkensRoel JanssenSam de BlankChris J de WitteJohn W M MartensMaurice P H M JansenMartijn P LolkemaWigard P KloostermanPublished in: Genome medicine (2021)
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 .
Keyphrases
- circulating tumor
- prostate cancer
- copy number
- high grade
- cell free
- circulating tumor cells
- radical prostatectomy
- single molecule
- real time pcr
- loop mediated isothermal amplification
- single cell
- high throughput
- small molecule
- papillary thyroid
- low grade
- case report
- dna methylation
- squamous cell
- gene expression
- solid state
- affordable care act
- label free
- young adults
- quantum dots
- benign prostatic hyperplasia