Accurate detection of circulating tumor DNA using nanopore consensus sequencing
| Autor: | Marcozzi, Alessio, Jager, Myrthe, Elferink, Martin, Straver, Roy, van Ginkel, Joost H., Peltenburg, Boris, Chen, Li-Ting, Renkens, Ivo, van Kuik, Joyce, Terhaard, Chris, de Bree, Remco, Devriese, Lot A., Willems, Stefan M., Kloosterman, Wigard P., de Ridder, Jeroen |
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| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | npj Genomic Medicine, Vol 6, Iss 1, Pp 1-11 (2021) npj Genomic Medicine, 6(1):106. NATURE PORTFOLIO NPJ Genomic Medicine |
| ISSN: | 2056-7944 |
| Popis: | Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ~60×, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows. |
| Databáze: | OpenAIRE |
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