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

by van Dessel, Lisanne F. , Jansen, Maurice P. H. M. , Kloosterman, Wigard P. , de Jong, Anouk C. , Janssen, Roel , de Blank, Sam , Renkens, Ivo , de Witte, Chris J. , Helmijr, Jean C. A. , van Roosmalen, Markus J. , Martens, John W. M. , Valle-Inclan, Jose Espejo , Stangl, Christina , Lolkema, Martijn P.

in Bioinformatics / Biomarkers / Biomarkers, Tumor / Biomedical and Life Sciences / Biomedicine / Biopsy / Cancer / Cancer patients / Cancer Research / Care and treatment / Circulating Tumor DNA / Computational Biology - methods / DNA / DNA sequencing / Female / Genetic aspects / Genomes / Genomic Structural Variation / Genomics / Human Genetics / Humans / Liquid biopsies / Liquid Biopsy - methods / Male / Medicine/Public Health / Metabolomics / Metastases / Metastasis / Method / Methods / Molecular Diagnostic Techniques - methods / Molecular Diagnostic Techniques - standards / Nanopore / Nanopore Sequencing / Neoplasms - diagnosis / Neoplasms - genetics / Nucleotide sequencing / Organ Specificity - genetics / Ovarian cancer / Patient monitoring equipment / Patients / Phenols / Polymerase chain reaction / Prostate cancer / Real-Time Polymerase Chain Reaction / Reproducibility of Results / Sensitivity and Specificity / Sequence Analysis, DNA / Structural variation / Systems Biology / Whole genome sequencing

2021

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

2021

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

2021

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Journal Article

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

van Dessel, Lisanne F.,

Jansen, Maurice P. H. M.,

Kloosterman, Wigard P.,

de Jong, Anouk C.,

Janssen, Roel,

de Blank, Sam,

Renkens, Ivo,

de Witte, Chris J.,

Helmijr, Jean C. A.,

van Roosmalen, Markus J.,

Martens, John W. M.,

Valle-Inclan, Jose Espejo,

Stangl, Christina,

Lolkema, Martijn P.

2021

Overview

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 .

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Publisher

BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC

Subject

Bioinformatics

/ Biomarkers

/ Biomarkers, Tumor

/ Biomedical and Life Sciences

/ Biomedicine

/ Biopsy

/ Cancer