Comprehensive characterisation of cell-free tumour DNA in plasma and urine of patients with renal tumours

Author:

Smith Christopher GORCID,Moser Tina,Burge Johanna,Eldridge Matthew,Riediger Anja L,Mouliere FlorentORCID,Chandrananda Dineika,Heider KatrinORCID,Wan Jonathan CM,Warren Anne Y,Morris James,Hudecova Irena,Cooper Wendy N,Mitchell Thomas J,Gale Davina,Ruiz-Valdepenas Andrea,Klatte Tobias,Ursprung Stephan,Sala Evis,Riddick Antony CP,Aho Tevita F,Armitage James N,Perakis Samantha,Pichler Martin,Seles Maximilian,Wcislo Gabriel,Welsh Sarah J,Matakidou Athena,Eisen Tim,Massie Charles E,Rosenfeld Nitzan,Heitzer EllenORCID,Stewart Grant DORCID

Abstract

AbstractCell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of cancers but its utility in renal cell cancer (RCC) has not been established. Here, untargeted and targeted sequencing methods, applied to two independent cohorts of renal tumour patients (n=90), were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ∼33%. A sensitive personalised approach, applied to plasma and urine from select patients improved detection to ∼50%, including in patients with early-stage and even benign lesions.A machine-learning based model predicted detection, potentially offering a means of triaging samples for personalised analysis. In addition, with limited data we observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than tissue biopsy. Furthermore, longitudinal sampling of >200 plasma samples revealed that ctDNA can track disease course. Additional datasets will be required to validate these findings.Overall, our data highlight RCC as a ctDNA-low malignancy, but indicate potential clinical utility provided improvement in detection approaches.One sentence summaryComplementary sequencing methods show that cell-free tumour DNA levels are low in renal cancer though, via various strategies, may still be informative.

Publisher

Cold Spring Harbor Laboratory

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