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

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

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 hig...

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Main Authors: Jose Espejo Valle-Inclan, Christina Stangl, Anouk C. de Jong, Lisanne F. van Dessel, Markus J. van Roosmalen, Jean C. A. Helmijr, Ivo Renkens, Roel Janssen, Sam de Blank, Chris J. de Witte, John W. M. Martens, Maurice P. H. M. Jansen, Martijn P. Lolkema, Wigard P. Kloosterman
Format: Article
Language:English
Published: BMC 2021-05-01
Series:Genome Medicine
Subjects:
Genomics
Liquid biopsies
Nanopore
Cancer
Structural variation
Online Access:https://doi.org/10.1186/s13073-021-00899-7
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spelling doaj-dc2d84df5339442da6944319858a489d2021-05-23T11:10:18ZengBMCGenome Medicine1756-994X2021-05-0113111410.1186/s13073-021-00899-7Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patientsJose Espejo Valle-Inclan0Christina Stangl1Anouk C. de Jong2Lisanne F. van Dessel3Markus J. van Roosmalen4Jean C. A. Helmijr5Ivo Renkens6Roel Janssen7Sam de Blank8Chris J. de Witte9John W. M. Martens10Maurice P. H. M. Jansen11Martijn P. Lolkema12Wigard P. Kloosterman13Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Oncology, Erasmus MC Cancer InstituteDepartment of Medical Oncology, Erasmus MC Cancer InstituteDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Oncology, Erasmus MC Cancer InstituteDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityDepartment of Medical Oncology, Erasmus MC Cancer InstituteDepartment of Medical Oncology, Erasmus MC Cancer InstituteDepartment of Medical Oncology, Erasmus MC Cancer InstituteDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht UniversityAbstract 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 .https://doi.org/10.1186/s13073-021-00899-7GenomicsLiquid biopsiesNanoporeCancerStructural variation
collection DOAJ
language English
format Article
sources DOAJ
author Jose Espejo Valle-Inclan
Christina Stangl
Anouk C. de Jong
Lisanne F. van Dessel
Markus J. van Roosmalen
Jean C. A. Helmijr
Ivo Renkens
Roel Janssen
Sam de Blank
Chris J. de Witte
John W. M. Martens
Maurice P. H. M. Jansen
Martijn P. Lolkema
Wigard P. Kloosterman
spellingShingle Jose Espejo Valle-Inclan
Christina Stangl
Anouk C. de Jong
Lisanne F. van Dessel
Markus J. van Roosmalen
Jean C. A. Helmijr
Ivo Renkens
Roel Janssen
Sam de Blank
Chris J. de Witte
John W. M. Martens
Maurice P. H. M. Jansen
Martijn P. Lolkema
Wigard P. Kloosterman
Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
Genome Medicine
Genomics
Liquid biopsies
Nanopore
Cancer
Structural variation
author_facet Jose Espejo Valle-Inclan
Christina Stangl
Anouk C. de Jong
Lisanne F. van Dessel
Markus J. van Roosmalen
Jean C. A. Helmijr
Ivo Renkens
Roel Janssen
Sam de Blank
Chris J. de Witte
John W. M. Martens
Maurice P. H. M. Jansen
Martijn P. Lolkema
Wigard P. Kloosterman
author_sort Jose Espejo Valle-Inclan
title Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
title_short Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
title_full Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
title_fullStr Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
title_full_unstemmed Optimizing Nanopore sequencing-based detection of structural variants enables individualized circulating tumor DNA-based disease monitoring in cancer patients
title_sort optimizing nanopore sequencing-based detection of structural variants enables individualized circulating tumor dna-based disease monitoring in cancer patients
publisher BMC
series Genome Medicine
issn 1756-994X
publishDate 2021-05-01
description 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 .
topic Genomics
Liquid biopsies
Nanopore
Cancer
Structural variation
url https://doi.org/10.1186/s13073-021-00899-7
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