Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients
Abstract 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 gu...
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| Language: | English |
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Springer Nature
2021-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202012881 |
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| author | Florent Mouliere Christopher G Smith Katrin Heider Jing Su Ymke van der Pol Mareike Thompson James Morris Jonathan C M Wan Dineika Chandrananda James Hadfield Marta Grzelak Irena Hudecova Dominique‐Laurent Couturier Wendy Cooper Hui Zhao Davina Gale Matthew Eldridge Colin Watts Kevin Brindle Nitzan Rosenfeld Richard Mair |
| author_facet | Florent Mouliere Christopher G Smith Katrin Heider Jing Su Ymke van der Pol Mareike Thompson James Morris Jonathan C M Wan Dineika Chandrananda James Hadfield Marta Grzelak Irena Hudecova Dominique‐Laurent Couturier Wendy Cooper Hui Zhao Davina Gale Matthew Eldridge Colin Watts Kevin Brindle Nitzan Rosenfeld Richard Mair |
| author_sort | Florent Mouliere |
| collection | DOAJ |
| description | Abstract 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 | Article |
| id | doaj-art-24159a2dc79e4f5a892d4bf85fcba5d8 |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-24159a2dc79e4f5a892d4bf85fcba5d82025-08-20T03:05:53ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-07-0113811410.15252/emmm.202012881Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patientsFlorent Mouliere0Christopher G Smith1Katrin Heider2Jing Su3Ymke van der Pol4Mareike Thompson5James Morris6Jonathan C M Wan7Dineika Chandrananda8James Hadfield9Marta Grzelak10Irena Hudecova11Dominique‐Laurent Couturier12Wendy Cooper13Hui Zhao14Davina Gale15Matthew Eldridge16Colin Watts17Kevin Brindle18Nitzan Rosenfeld19Richard Mair20Cancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Centre AmsterdamCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeDivision of Neurosurgery, Department of Clinical Neurosciences, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeAbstract 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.https://doi.org/10.15252/emmm.202012881cell‐free DNAcirculating tumor DNAfragmentomicsgliomasliquid biopsy |
| spellingShingle | Florent Mouliere Christopher G Smith Katrin Heider Jing Su Ymke van der Pol Mareike Thompson James Morris Jonathan C M Wan Dineika Chandrananda James Hadfield Marta Grzelak Irena Hudecova Dominique‐Laurent Couturier Wendy Cooper Hui Zhao Davina Gale Matthew Eldridge Colin Watts Kevin Brindle Nitzan Rosenfeld Richard Mair Fragmentation patterns and personalized sequencing of cell‐free DNA in urine and plasma of glioma patients EMBO Molecular Medicine cell‐free DNA circulating tumor DNA fragmentomics gliomas liquid biopsy |
| 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 | cell‐free DNA circulating tumor DNA fragmentomics gliomas liquid biopsy |
| url | https://doi.org/10.15252/emmm.202012881 |
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