The DNA methylation landscape of advanced prostate cancer

被引：0

作者：

Shuang G. Zhao

William S. Chen

Haolong Li

Adam Foye

Meng Zhang

Martin Sjöström

Rahul Aggarwal

Denise Playdle

Arnold Liao

Joshi J. Alumkal

Rajdeep Das

Jonathan Chou

Junjie T. Hua

Travis J. Barnard

Adina M. Bailey

Eric D. Chow

Marc D. Perry

Ha X. Dang

Rendong Yang

Ruhollah Moussavi-Baygi

Li Zhang

Mohammed Alshalalfa

S. Laura Chang

Kathleen E. Houlahan

Yu-Jia Shiah

Tomasz M. Beer

George Thomas

Kim N. Chi

Martin Gleave

Amina Zoubeidi

Robert E. Reiter

Matthew B. Rettig

Owen Witte

M. Yvonne Kim

Lawrence Fong

Daniel E. Spratt

Todd M. Morgan

Rohit Bose

Franklin W. Huang

Hui Li

Lisa Chesner

Tanushree Shenoy

Hani Goodarzi

Irfan A. Asangani

Shahneen Sandhu

Joshua M. Lang

Nupam P. Mahajan

Primo N. Lara

Christopher P. Evans

Phillip Febbo

机构：

[1] University of Michigan,Department of Radiation Oncology

[2] University of Michigan,Rogel Cancer Center

[3] University of California San Francisco,Department of Radiation Oncology

[4] University of California San Francisco,Helen Diller Family Comprehensive Cancer Center

[5] University of Michigan,Michigan Center for Translational Pathology

[6] Yale School of Medicine,Division of Hematology and Oncology, Department of Medicine

[7] University of California San Francisco,Department of Molecular and Medical Genetics

[8] Illumina Inc.,Princess Margaret Cancer Centre

[9] Knight Cancer Institute,Department of Biochemistry and Biophysics

[10] Oregon Health & Science University,Center for Advanced Technology

[11] Oregon Health & Science University,Department of Internal Medicine

[12] University Health Network,Siteman Cancer Center

[13] University of California San Francisco,Department of Medical Biophysics

[14] University of California San Francisco,Department of Human Genetics

[15] McDonnell Genome Institute,Division of Hematology/Medical Oncology, Department of Medicine

[16] Washington University,Department of Pathology

[17] Washington University,Vancouver Prostate Centre, Department of Urologic Sciences

[18] Washington University,Jonsson Comprehensive Cancer Center, Departments of Medicine and Urology

[19] The Hormel Institute,Department of Medicine

[20] University of Minnesota,Department of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine

[21] Ontario Institute for Cancer Research,Department of Neurological Surgery

[22] University of Toronto,Department of Urology

[23] Institute for Precision Health,Department of Urology

[24] UCLA,Department of Anatomy

[25] Oregon Health & Science University,Department of Cancer Biology

[26] Oregon Health & Science University,Peter MacCallum Cancer Centre

[27] University of British Columbia,Department of Medicine

[28] British Columbia Cancer Agency,Department of Surgery

[29] Vancouver Centre,Division of Hematology Oncology, Department of Internal Medicine

[30] University of California Los Angeles,Comprehensive Cancer Center

[31] VA Greater Los Angeles Healthcare System,Department of Urologic Surgery

[32] University of California Los Angeles,Department of Cancer Biology

[33] University of California San Francisco,Department of Pathology

[34] University of Michigan,Department of Pathology

[35] University of California San Francisco,Masonic Cancer Center

[36] University of California San Francisco,Department of Laboratory Medicine and Pathology

[37] University of Pennsylvania,Department of Pathology

[38] University of Melbourne,Department of Computational Medicine and Bioinformatics

[39] University of Wisconsin,Department of Biomedical Engineering

[40] Washington University,Department of Epidemiology and Biostatistics

[41] University of California Davis,undefined

[42] University of California Davis,undefined

[43] University of California Davis,undefined

[44] Thomas Jefferson University,undefined

[45] Duke University,undefined

[46] Netherlands Cancer Institute,undefined

[47] Oncode Institute,undefined

[48] University of Pittsburgh,undefined

[49] University of Minnesota,undefined

[50] University of Minnesota,undefined

来源：

Nature Genetics | 2020年 / 52卷

关键词：

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中图分类号：

学科分类号：

摘要：

Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes AR, MYC and ERG. Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions. This study is a large integrated study of whole-genome, whole-methylome and whole-transcriptome sequencing in metastatic cancer that provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer.

引用

页码：778 / 789

页数：11

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