The cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors

Sujun Chen, Jessica Petricca, Wenbin Ye, Jiansheng Guan, Yong Zeng, Nicholas Cheng, Linsey Gong, Shu Yi Shen, Junjie T. Hua, Megan Crumbaker, Michael Fraser, Stanley Liu, Scott V. Bratman, Theodorus Kwast, Trevor Pugh, Anthony M. Joshua, Daniel D. Carvalho, Kim N. Chi, Philip Awadalla, Guoli Ji (), Felix Feng (), Alexander W. Wyatt () and Housheng Hansen He ()
Additional contact information
Sujun Chen: University Health Network
Jessica Petricca: University Health Network
Wenbin Ye: University Health Network
Jiansheng Guan: University Health Network
Yong Zeng: University Health Network
Nicholas Cheng: University of Toronto
Linsey Gong: University Health Network
Shu Yi Shen: University Health Network
Junjie T. Hua: University of California
Megan Crumbaker: Kinghorn Cancer Centre, St Vincent’s Hospital
Michael Fraser: University Health Network
Stanley Liu: University of Toronto
Scott V. Bratman: University Health Network
Theodorus Kwast: University of Toronto
Trevor Pugh: University Health Network
Anthony M. Joshua: University of Toronto
Daniel D. Carvalho: University Health Network
Kim N. Chi: British Columbia Cancer Agency, Vancouver Centre
Philip Awadalla: Ontario Institute for Cancer Research
Guoli Ji: Xiamen University
Felix Feng: University of California
Alexander W. Wyatt: University of British Columbia
Housheng Hansen He: University Health Network

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensitive enrichment-based sequencing technology, we provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively. We show that the cell-free DNA methylome can capture variations beyond the tumor. A global hypermethylation in metastatic samples is observed, coupled with hypomethylation in the pericentromeric regions. Hypermethylation at the promoter of a glucocorticoid receptor gene NR3C1 is associated with a decreased immune signature. The cell-free DNA methylome is reflective of clinical outcomes and can distinguish different disease types with 0.989 prediction accuracy. Finally, we show the ability of predicting copy number alterations from the data, providing opportunities for joint genetic and epigenetic analysis on limited biological samples.

Date: 2022
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DOI: 10.1038/s41467-022-34012-2

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