London Calling 2023: The potential application of nanopore sequencing for liquid biopsy analysis in children with cancer

Paediatric cancers are the leading cause of death in children post infancy. Analysis of cell-free DNA (cfDNA) to detect circulating tumour-derived DNA (ctDNA) may offer a powerful, minimally invasive tool for diagnosis and comprehensive molecular tumour profiling. Current ctDNA approaches are limited in sensitivity, specificity, scalability, turnaround time, and cost, hindering their implementation into standard clinical care. Here, we exploit whole-genome nanopore sequencing for the multi-modal analysis of cfDNA in paediatric cancer patients. Using liquid biopsy samples from the Stratified Medicine Paediatrics study, we demonstrate the utility of nanopore sequencing to detect clinically relevant somatic aberrations, highly concordant with those detected using matched low-pass Illumina whole-genome sequencing. Additionally, nanopore sequencing allowed read-out of methylation profiles from cfDNA, facilitating tissue-of-origin and oncotype characterisation. Finally, longitudinal monitoring using nanopore sequencing correlated with disease burden and was predictive of disease recurrence, illustrating the strong potential of nanopore-based approaches for clinical disease management in children with cancer.