The landscape of N6-methyladenosine in localized primary prostate cancer

被引：0

作者：

Xin Xu ^{[1
]}

Helen Zhu ^{[1
]}

Rupert Hugh-White ^{[2
]}

Julie Livingstone ^{[3
]}

Stefan Eng ^{[4
]}

Nicole Zeltser ^{[5
]}

Yujuan Wang ^{[6
]}

Kinga Pajdzik ^{[7
]}

Sujun Chen ^{[4
]}

Kathleen E. Houlahan ^{[5
]}

Wenqin Luo ^{[6
]}

Shun Liu ^{[7
]}

Xi Xu ^{[4
]}

Minzhi Sheng ^{[5
]}

Wang Yuan Guo ^{[6
]}

Jaron Arbet ^{[7
]}

Yuxi Song ^{[4
]}

Miranda Wang ^{[5
]}

Yong Zeng ^{[6
]}

Shiyan Wang ^{[7
]}

Guanghui Zhu ^{[1
]}

Tingxiao Gao ^{[8
]}

Wei Chen ^{[9
]}

Xinpei Ci ^{[1
]}

Wenjie Xu ^{[2
]}

Kexin Xu ^{[21
]}

Michele Orain ^{[2
]}

Valerie Picard ^{[3
]}

Helene Hovington ^{[4
]}

Alain Bergeron ^{[5
]}

Louis Lacombe ^{[6
]}

Bernard Têtu ^{[7
]}

Yves Fradet ^{[1
]}

Mathieu Lupien ^{[10
]}

Gong-Hong Wei ^{[8
]}

Marianne Koritzinsky ^{[9
]}

Robert G. Bristow ^{[1
]}

Neil E. Fleshner ^{[2
]}

Xue Wu ^{[11
]}

Yang Shao ^{[1
]}

Chuan He ^{[4
]}

Alejandro Berlin ^{[5
]}

Theodorus van der Kwast ^{[6
]}

Hon Leong ^{[7
]}

Paul C. Boutros ^{[4
]}

Housheng Hansen He ^{[5
]}

机构：

[1] University Health Network,Princess Margaret Cancer Center

[2] University of Toronto,Department of Medical Biophysics

[3] Vector Institute,Department of Urology

[4] University of California,Institute for Precision Health

[5] Los Angeles,Jonsson Comprehensive Cancer Centre

[6] University of California,Department of Human Genetics

[7] Los Angeles,Department of Chemistry

[8] University of California,Howard Hughes Medical Institute

[9] Los Angeles,Department of Urology, Sir Run Run Shaw Hospital

[10] University of California,MOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Fudan University Shanghai Cancer Center

[11] Los Angeles,Department of Molecular Medicine

[12] the University of Chicago,State Key Laboratory of Common Mechanism Research for Major Disease, Suzhou Institute of Systems Medicine

[13] the University of Chicago,Division of Cancer Sciences

[14] Zhejiang University School of Medicine,Geneseeq Research Institute

[15] Sunnybrook Research Institute,School of Public Health

[16] Shanghai Medical College of Fudan University,Department of Pharmacology and Toxicology

[17] University of Texas Health Science Center at San Antonio,West China School of Public Health, West China Fourth Hospital and State Key Laboratory of Biotherapy

[18] Research Centre of CHU de Québec-Université Laval,Institute of Precision Medicine, First Affiliated Hospital

[19] Chinese Academy of Medical Sciences and Peking Union Medical College,Department of Respiratory and Critical Care Medicine

[20] University of Manchester,undefined

[21] Christie NHS Trust and CRUK Manchester Institute and Cancer Centre,undefined

[22] Geneseeq Technology lnc.,undefined

[23] Nanjing Medical University,undefined

[24] University of Toronto,undefined

[25] Sichuan University,undefined

[26] Sun Yat-sen University,undefined

[27] the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University,undefined

来源：

Nature Genetics | 2025年 / 57卷 / 4期

关键词：

D O I：

10.1038/s41588-025-02128-y

中图分类号：

学科分类号：

摘要：

N6-methyladenosine (m6A), the most abundant internal RNA modification in humans, regulates most aspects of RNA processing. Prostate cancer is characterized by widespread transcriptomic dysregulation; therefore, we characterized the m6A landscape of 162 localized prostate tumors with matched DNA, RNA and protein profiling. m6A abundance varied dramatically across tumors, with global patterns emerging via complex germline–somatic cooperative regulation. Individual germline polymorphisms regulated m6A abundance, cooperating with somatic mutation of cancer driver genes and m6A regulators. The resulting complex patterns were associated with prognostic clinical features and established the biomarker potential of global and locus-specific m6A patterns. Tumor hypoxia dysregulates m6A profiles, bridging prior genomic and proteomic observations. Specific m6A sites, such as those in VCAN, drive disease aggression, associating with poor outcomes, tumor growth and metastasis. m6A dysregulation is thus associated with key events in the natural history of prostate cancer: germline risk, microenvironmental dysregulation, somatic mutation and metastasis.

引用

页码：934 / 948

页数：14

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