Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes

Pier Vitale Nuzzo; Jacob E Berchuck; Keegan Korthauer; Sandor Spisak; Amin H Nassar; Sarah Abou Alaiwi; Ankur Chakravarthy; Shu Yi Shen; Ziad Bakouny; Francesco Boccardo; John Steinharter; Gabrielle Bouchard; Catherine R Curran; Wenting Pan; Sylvan C Baca; Ji-Heui Seo; Gwo-Shu Mary Lee; M Dror Michaelson; Steven L Chang; Sushrut S Waikar; Guru Sonpavde; Rafael A Irizarry; Mark Pomerantz; Daniel D De Carvalho; Toni K Choueiri; Matthew L Freedman

doi:10.1038/s41591-020-0933-1

Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes

Nat Med. 2020 Jul;26(7):1041-1043. doi: 10.1038/s41591-020-0933-1. Epub 2020 Jun 22.

Authors

Pier Vitale Nuzzo^#^{1

2

3}, Jacob E Berchuck^#^{1

2}, Keegan Korthauer^#^{4

5}, Sandor Spisak^#², Amin H Nassar^{1

2}, Sarah Abou Alaiwi^{1

2}, Ankur Chakravarthy⁶, Shu Yi Shen⁶, Ziad Bakouny¹, Francesco Boccardo^{3

7}, John Steinharter¹, Gabrielle Bouchard¹, Catherine R Curran¹, Wenting Pan¹, Sylvan C Baca^{1

2

8}, Ji-Heui Seo^{1

2}, Gwo-Shu Mary Lee^{1

2}, M Dror Michaelson⁹, Steven L Chang¹⁰, Sushrut S Waikar^{11

12}, Guru Sonpavde¹, Rafael A Irizarry^{13

14}, Mark Pomerantz^{1

2}, Daniel D De Carvalho^{6

15}, Toni K Choueiri^{16

17}, Matthew L Freedman^{18

19

20}

Affiliations

¹ Department of Medical Oncology, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
² Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
³ Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genoa, Genoa, Italy.
⁴ Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
⁵ BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
⁶ Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
⁷ Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, Genoa, Italy.
⁸ The Eli and Edythe L. Broad Institute, Cambridge, MA, USA.
⁹ Massachusetts General Hospital Cancer Center, Hematology/Oncology, Boston, MA, USA.
¹⁰ Division of Urology, Brigham and Women's Hospital, Boston, MA, USA.
¹¹ Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹² Section of Nephrology, Boston University Medical Center, Boston, MA, USA.
¹³ Department of Biostatistics, Harvard University, Cambridge, MA, USA.
¹⁴ Department of Data Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Department of Medical Oncology, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. toni_choueiri@dfci.harvard.edu.
¹⁷ The Eli and Edythe L. Broad Institute, Cambridge, MA, USA. toni_choueiri@dfci.harvard.edu.
¹⁸ Department of Medical Oncology, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. mfreedman@partners.org.
¹⁹ Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. mfreedman@partners.org.
²⁰ The Eli and Edythe L. Broad Institute, Cambridge, MA, USA. mfreedman@partners.org.

^# Contributed equally.

Abstract

Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a highly sensitive assay capable of detecting early-stage tumors. We report accurate classification of patients across all stages of renal cell carcinoma (RCC) in plasma (area under the receiver operating characteristic (AUROC) curve of 0.99) and demonstrate the validity of this assay to identify patients with RCC using urine cell-free DNA (cfDNA; AUROC of 0.86).

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Biomarkers, Tumor / genetics
Carcinoma, Renal Cell / blood
Carcinoma, Renal Cell / diagnosis*
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / urine
Cell-Free Nucleic Acids / blood
Cell-Free Nucleic Acids / genetics
Cell-Free Nucleic Acids / urine
DNA Methylation / genetics*
Early Detection of Cancer*
Epigenome / genetics
High-Throughput Nucleotide Sequencing
Humans

Substances

Biomarkers, Tumor
Cell-Free Nucleic Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding