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Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients
Glioma‐derived cell‐free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma‐derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by a...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350897/ https://www.ncbi.nlm.nih.gov/pubmed/34291583 http://dx.doi.org/10.15252/emmm.202012881 |
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author | Mouliere, Florent Smith, Christopher G Heider, Katrin Su, Jing van der Pol, Ymke Thompson, Mareike Morris, James Wan, Jonathan C M Chandrananda, Dineika Hadfield, James Grzelak, Marta Hudecova, Irena Couturier, Dominique‐Laurent Cooper, Wendy Zhao, Hui Gale, Davina Eldridge, Matthew Watts, Colin Brindle, Kevin Rosenfeld, Nitzan Mair, Richard |
author_facet | Mouliere, Florent Smith, Christopher G Heider, Katrin Su, Jing van der Pol, Ymke Thompson, Mareike Morris, James Wan, Jonathan C M Chandrananda, Dineika Hadfield, James Grzelak, Marta Hudecova, Irena Couturier, Dominique‐Laurent Cooper, Wendy Zhao, Hui Gale, Davina Eldridge, Matthew Watts, Colin Brindle, Kevin Rosenfeld, Nitzan Mair, Richard |
author_sort | Mouliere, Florent |
collection | PubMed |
description | Glioma‐derived cell‐free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma‐derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by analysis of matched tumor biopsies. By sequencing cfDNA across thousands of mutations, identified individually in each patient’s tumor, we detected tumor‐derived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.4 × 10(−3), 3.1 × 10(−5), and 4.7 × 10(−5), respectively. We identified a shift in the size distribution of tumor‐derived cfDNA fragments in these body fluids. We further analyzed cfDNA fragment sizes using whole‐genome sequencing, in urine samples from 35 glioma patients, 27 individuals with non‐malignant brain disorders, and 26 healthy individuals. cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with non‐malignant brain disorders (P = 1.7 × 10(−2)) and healthy individuals (P = 5.2 × 10(−9)). Machine learning models integrating fragment length could differentiate urine samples from glioma patients (AUC = 0.80–0.91) suggesting possibilities for truly non‐invasive cancer detection. |
format | Online Article Text |
id | pubmed-8350897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83508972021-08-15 Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients Mouliere, Florent Smith, Christopher G Heider, Katrin Su, Jing van der Pol, Ymke Thompson, Mareike Morris, James Wan, Jonathan C M Chandrananda, Dineika Hadfield, James Grzelak, Marta Hudecova, Irena Couturier, Dominique‐Laurent Cooper, Wendy Zhao, Hui Gale, Davina Eldridge, Matthew Watts, Colin Brindle, Kevin Rosenfeld, Nitzan Mair, Richard EMBO Mol Med Articles Glioma‐derived cell‐free DNA (cfDNA) is challenging to detect using liquid biopsy because quantities in body fluids are low. We determined the glioma‐derived DNA fraction in cerebrospinal fluid (CSF), plasma, and urine samples from patients using sequencing of personalized capture panels guided by analysis of matched tumor biopsies. By sequencing cfDNA across thousands of mutations, identified individually in each patient’s tumor, we detected tumor‐derived DNA in the majority of CSF (7/8), plasma (10/12), and urine samples (10/16), with a median tumor fraction of 6.4 × 10(−3), 3.1 × 10(−5), and 4.7 × 10(−5), respectively. We identified a shift in the size distribution of tumor‐derived cfDNA fragments in these body fluids. We further analyzed cfDNA fragment sizes using whole‐genome sequencing, in urine samples from 35 glioma patients, 27 individuals with non‐malignant brain disorders, and 26 healthy individuals. cfDNA in urine of glioma patients was significantly more fragmented compared to urine from patients with non‐malignant brain disorders (P = 1.7 × 10(−2)) and healthy individuals (P = 5.2 × 10(−9)). Machine learning models integrating fragment length could differentiate urine samples from glioma patients (AUC = 0.80–0.91) suggesting possibilities for truly non‐invasive cancer detection. John Wiley and Sons Inc. 2021-07-22 2021-08-09 /pmc/articles/PMC8350897/ /pubmed/34291583 http://dx.doi.org/10.15252/emmm.202012881 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Mouliere, Florent Smith, Christopher G Heider, Katrin Su, Jing van der Pol, Ymke Thompson, Mareike Morris, James Wan, Jonathan C M Chandrananda, Dineika Hadfield, James Grzelak, Marta Hudecova, Irena Couturier, Dominique‐Laurent Cooper, Wendy Zhao, Hui Gale, Davina Eldridge, Matthew Watts, Colin Brindle, Kevin Rosenfeld, Nitzan Mair, Richard Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients |
title | Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients |
title_full | Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients |
title_fullStr | Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients |
title_full_unstemmed | Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients |
title_short | Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients |
title_sort | fragmentation patterns and personalized sequencing of cell‐free dna in urine and plasma of glioma patients |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350897/ https://www.ncbi.nlm.nih.gov/pubmed/34291583 http://dx.doi.org/10.15252/emmm.202012881 |
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