Real‐time analysis of the cancer genome and fragmentome from plasma and urine cell‐free DNA using nanopore sequencing

Autor: Ymke van der Pol, Normastuti Adhini Tantyo, Nils Evander, Anouk E Hentschel, Birgit MM Wever, Jip Ramaker, Sanne Bootsma, Marieke F Fransen, Kristiaan J Lenos, Louis Vermeulen, Famke L Schneiders, Idris Bahce, Jakko A Nieuwenhuijzen, Renske DM Steenbergen, D Michiel Pegtel, Norbert Moldovan, Florent Mouliere
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 15, Iss 12, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202217282
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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