Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

Christopher G Smith, Tina Moser, Florent Mouliere, Johanna Field-Rayner, Matthew Eldridge, Anja L Riediger, Dineika Chandrananda, Katrin Heider, Jonathan C M Wan, Anne Y Warren, James Morris, Irena Hudecova, Wendy N Cooper, Thomas J Mitchell, Davina Gale, Andrea Ruiz-Valdepenas, Tobias Klatte, Stephan Ursprung, Evis Sala, Antony C P RiddickTevita F Aho, James N Armitage, Samantha Perakis, Martin Pichler, Maximilian Seles, Gabriel Wcislo, Sarah J Welsh, Athena Matakidou, Tim Eisen, Charles E Massie, Nitzan Rosenfeld, Ellen Heitzer, Grant D Stewart

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.

METHODS: Here, a combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n = 91) with various renal tumor subtypes, were used to determine ctDNA content in plasma and urine.

RESULTS: Our data revealed lower plasma ctDNA levels in RCC relative to other cancers of similar size and stage, with untargeted detection in 27.5% of patients from both cohorts. A sensitive personalized approach, applied to plasma and urine from select patients (n = 22) improved detection to ~ 50%, including in patients with early-stage disease and even benign lesions. Detection in plasma, but not urine, was more frequent amongst patients with larger tumors and in those patients with venous tumor thrombus. With data from one extensively characterized patient, we observed that plasma and, for the first time, urine ctDNA may better represent tumor heterogeneity than a single tissue biopsy. Furthermore, in a subset of patients (n = 16), longitudinal sampling revealed that ctDNA can track disease course and may pre-empt radiological identification of minimal residual disease or disease progression on systemic therapy. Additional datasets will be required to validate these findings.

CONCLUSIONS: These data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches.

Original languageEnglish
Article number23
Pages (from-to)23
JournalGenome Medicine
Issue number1
Publication statusPublished - 28 Feb 2020

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