Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients
© 2021 The Authors. Published under the terms of the CC BY 4.0 license..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
EMBO molecular medicine - 13(2021), 8 vom: 09. Aug., Seite e12881 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mouliere, Florent [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers, Tumor |
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| Anmerkungen: |
Date Completed 25.10.2021 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/emmm.202012881 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM328365572 |
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| 245 | 1 | 0 | |a Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients |
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| 520 | |a © 2021 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a cell-free DNA | |
| 650 | 4 | |a circulating tumor DNA | |
| 650 | 4 | |a fragmentomics | |
| 650 | 4 | |a gliomas | |
| 650 | 4 | |a liquid biopsy | |
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| 700 | 1 | |a Smith, Christopher G |e verfasserin |4 aut | |
| 700 | 1 | |a Heider, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a van der Pol, Ymke |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, Mareike |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, James |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Jonathan C M |e verfasserin |4 aut | |
| 700 | 1 | |a Chandrananda, Dineika |e verfasserin |4 aut | |
| 700 | 1 | |a Hadfield, James |e verfasserin |4 aut | |
| 700 | 1 | |a Grzelak, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Hudecova, Irena |e verfasserin |4 aut | |
| 700 | 1 | |a Couturier, Dominique-Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Wendy |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Gale, Davina |e verfasserin |4 aut | |
| 700 | 1 | |a Eldridge, Matthew |e verfasserin |4 aut | |
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| 700 | 1 | |a Brindle, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenfeld, Nitzan |e verfasserin |4 aut | |
| 700 | 1 | |a Mair, Richard |e verfasserin |4 aut | |
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