Real-time analysis of the cancer genome and fragmentome from plasma and urine cell-free DNA using nanopore sequencing.
cancer
cell-free DNA
fragmentomics
liquid biopsy
nanopore sequencing
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
revised:
13
10
2023
received:
11
12
2022
accepted:
17
10
2023
medline:
11
12
2023
pubmed:
9
11
2023
entrez:
9
11
2023
Statut:
ppublish
Résumé
Cell-free DNA (cfDNA) can be isolated and sequenced from blood and/or urine of cancer patients. Conventional short-read sequencing lacks deployability and speed and can be biased for short cfDNA fragments. Here, we demonstrate that with Oxford Nanopore Technologies (ONT) sequencing we can achieve delivery of genomic and fragmentomic data from liquid biopsies. Copy number aberrations and cfDNA fragmentation patterns can be determined in less than 24 h from sample collection. The tumor-derived cfDNA fraction calculated from plasma of lung cancer patients and urine of bladder cancer patients was highly correlated (R = 0.98) with the tumor fraction calculated from short-read sequencing of the same samples. cfDNA size profile, fragmentation patterns, fragment-end composition, and nucleosome profiling near transcription start sites in plasma and urine exhibited the typical cfDNA features. Additionally, a high proportion of long tumor-derived cfDNA fragments (> 300 bp) are recovered in plasma and urine using ONT sequencing. ONT sequencing is a cost-effective, fast, and deployable approach for obtaining genomic and fragmentomic results from liquid biopsies, allowing the analysis of previously understudied cfDNA populations.
Identifiants
pubmed: 37942753
doi: 10.15252/emmm.202217282
pmc: PMC10701599
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
DNA
9007-49-2
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e17282Subventions
Organisme : KWF Kankerbestrijding (DCS)
ID : 12822
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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