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

被引:35
作者
Chen, Sujun [1 ,2 ,3 ,4 ]
Petricca, Jessica [1 ,2 ]
Ye, Wenbin [1 ,5 ,6 ]
Guan, Jiansheng [1 ,7 ]
Zeng, Yong [1 ]
Cheng, Nicholas [2 ]
Gong, Linsey [1 ,2 ]
Shen, Shu Yi
Hua, Junjie T. [8 ,9 ]
Crumbaker, Megan [10 ]
Fraser, Michael [1 ]
Liu, Stanley [2 ,11 ,12 ]
Bratman, Scott, V [1 ,2 ]
van der Kwast, Theodorus [2 ,13 ]
Pugh, Trevor [1 ,2 ]
Joshua, Anthony M. [13 ]
De Carvalho, Daniel D. [1 ,2 ]
Chi, Kim N. [14 ]
Awadalla, Philip [15 ]
Ji, Guoli [5 ,6 ]
Feng, Felix [8 ,9 ,16 ,17 ]
Wyatt, Alexander W. [18 ]
He, Housheng Hansen [1 ,2 ]
机构
[1] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada
[3] Sichuan Univ, West China Sch Publ Hlth, West China Hosp 4, Chengdu, Peoples R China
[4] Sichuan Univ, State Key Lab Biotherapy, Chengdu, Peoples R China
[5] Xiamen Univ, Dept Automat, Xiamen, Fujian, Peoples R China
[6] Xiamen Univ, Natl Inst Data Sci Hlth & Med, Xiamen, Fujian, Peoples R China
[7] Xiamen Univ Technol, Coll Elect Engn & Automat, Xiamen, Fujian, Peoples R China
[8] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94115 USA
[9] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA
[10] St Vincents Hosp, Dept Med Oncol, Kinghorn Canc Ctr, Sydney, NSW, Australia
[11] Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON, Canada
[12] Sunnybrook Odette Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada
[13] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada
[14] British Columbia Canc Agcy, Vancouver Ctr, Vancouver, BC, Canada
[15] Ontario Inst Canc Res, Toronto, ON, Canada
[16] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA 94143 USA
[17] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94110 USA
[18] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大创新基金会;
关键词
CPG ISLAND HYPERMETHYLATION; ANDROGEN RECEPTOR; PLASMA DNA; GLUCOCORTICOID-RECEPTOR; CANCER; METHYLATION; HYPOMETHYLATION; SURVIVAL; ENZALUTAMIDE; ABIRATERONE;
D O I
10.1038/s41467-022-34012-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Metastatic prostate cancer can be difficult to biopsy and characterise. Here, the authors use cell-free DNA methylation analysis to illustrate changes in hypermethylation in metastatic disease. 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.
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页数:14
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