Investigators have independently validated an assay for tumor-derived plasma cell-free DNA (cfDNA) that detects early-stage renal cell carcinoma (RCC) and demonstrated for the first time that this assay can accurately detect RCC by measuring urine cfDNA.

The assay is called cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq). It is an enrichment-based method for comprehensive cfDNA methylation profiling, the investigators explained. Based on the new findings, investigators say the assay could be useful for RCC screening if further studies firmly establish its reliability.

“After training on larger datasets and performing prospective validation, this method could ultimately reduce morbidity and mortality through early and accurate detection of RCC and other cancers,” Pier Vitale Nuzzo, MD, of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, and colleagues wrote in a report in Nature Medicine.

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The investigators performed cfMeDIP-seq on samples from 99 patients with stage I-IV RCC cases, 21 patients with stage IV urothelial bladder cancer, and 28 healthy, cancer-free controls. Two-thirds of the patients with RCC had localized disease.

Based on plasma analyses, the assay differentiated patients with RCC from controls with near-perfect (99%) accuracy. When performed on urine samples, the assay identified patients with RCC with 86% accuracy.

“While urine-based classification was not as accurate as plasma-based classification, we believe that performance can be improved through technical and computational optimization, such as size selection of cfDNA to enrich for tumor-derived  DNA and utilizing tumor methylation data to inform cfDNA methylation analysis.”

As for the potential usefulness of the assay in clinical practice, the authors noted, “An accurate, highly sensitive and specific noninvasive test, alone or in combination with imaging, could transform clinical management by enabling early detection of RCC and reducing unnecessary kidney biopsies and nephrectomies.”


Nuzzo PV, Berchuck JE, Korthauer K, et al. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med. 2020;26(7):1041-1043. doi:10.1038/s41591-020-0933-1