TY - JOUR T1 - Accurate detection of circulating tumor DNA using nanopore consensus sequencing JF - bioRxiv DO - 10.1101/2020.07.14.202010 SP - 2020.07.14.202010 AU - Alessio Marcozzi AU - Myrthe Jager AU - Martin Elferink AU - Roy Straver AU - Joost H. van Ginkel AU - Boris Peltenburg AU - Li-Ting Chen AU - Ivo Renkens AU - Joyce van Kuik AU - Chris Terhaard AU - Remco de Bree AU - Lot A. Devriese AU - Stefan M. Willems AU - Wigard P. Kloosterman AU - Jeroen de Ridder Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/15/2020.07.14.202010.abstract N2 - 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 ∼60x, 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 point-of-care clinical workflows.Competing Interest StatementThe authors declare the following financial competing interest: A.M., R.S., W.P.K., and J.d.R filed patents and A.M., W.P.K., and J.d.R founded a company (Cyclomics) based on CyclomicsSeq. ER -