The landscape of N6-methyladenosine in localized primary prostate cancer

被引：0

作者：

Xu, Xin ^{[1
]}

Zhu, Helen ^{[1
,2
,3
]}

Hugh-White, Rupert ^{[4
,5
,6
,7
]}

Livingstone, Julie ^{[4
,5
,6
,7
]}

Eng, Stefan ^{[4
,5
,6
,7
]}

Zeltser, Nicole ^{[4
,5
,6
,7
]}

Wang, Yujuan ^{[1
]}

Pajdzik, Kinga ^{[8
,9
]}

Chen, Sujun ^{[1
,2
,22
,23
]}

Houlahan, Kathleen E. ^{[2
,3
,4
,5
,6
,7
]}

Luo, Wenqin ^{[1
,10
]}

Liu, Shun ^{[8
,9
]}

Xu, Xi ^{[1
]}

Sheng, Minzhi ^{[2
,11
]}

Guo, Wang Yuan ^{[1
]}

Arbet, Jaron ^{[4
,5
,6
,7
]}

Song, Yuxi ^{[4
,5
,6
,7
]}

Wang, Miranda ^{[1
]}

Zeng, Yong ^{[1
]}

Wang, Shiyan ^{[1
,24
]}

Zhu, Guanghui ^{[1
,2
,22
,23
]}

Gao, Tingxiao ^{[1
,2
]}

Chen, Wei ^{[1
,25
]}

Ci, Xinpei ^{[1
]}

Xu, Wenjie ^{[12
,13
]}

Xu, Kexin ^{[14
]}

Orain, Michele ^{[15
]}

Picard, Valerie ^{[15
]}

Hovington, Helene ^{[15
]}

Bergeron, Alain ^{[15
]}

Lacombe, Louis ^{[15
]}

Tetu, Bernard ^{[15
]}

Fradet, Yves ^{[15
]}

Lupien, Mathieu ^{[1
,2
]}

Wei, Gong-Hong ^{[12
,13
,16
]}

Koritzinsky, Marianne ^{[1
,2
]}

Bristow, Robert G. ^{[17
,18
]}

Fleshner, Neil E. ^{[1
]}

Wu, Xue ^{[19
]}

Shao, Yang ^{[19
,20
]}

He, Chuan ^{[8
,9
]}

Berlin, Alejandro ^{[1
]}

van der Kwast, Theodorus ^{[1
]}

Leong, Hon ^{[2
,11
]}

Boutros, Paul C. ^{[2
,3
,4
,5
,6
,7
,21
]}

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] Vector Inst, Toronto, ON, Canada

[4] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

[7] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[8] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[9] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA

[10] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Urol, Hangzhou, Peoples R China

[11] Sunnybrook Res Inst, Toronto, ON, Canada

[12] Fudan Univ, Sch Basic Med Sci, MOE Key Lab Metab & Mol Med, Shanghai Med Coll, Shanghai, Peoples R China

[13] Fudan Univ, Shanghai Canc Ctr, Sch Basic Med Sci, Dept Biochem,Shanghai Med Coll, Shanghai, Peoples R China

[14] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX USA

[15] Univ Laval, Res Ctr, CHU Quebec, Quebec City, PQ, Canada

[16] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Common Mech Res Major Dis, Suzhou Inst Syst Med, Suzhou, Peoples R China

[17] Univ Manchester, Div Canc Sci, Manchester, Lancs, England

[18] Christie NHS Trust & & CRUK Manchester Inst, Manchester, England

[19] Geneseeq Technol lnc, Geneseeq Res Inst, Toronto, ON, Canada

[20] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Peoples R China

[21] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[22] Sichuan Univ, West China Hosp, West China Med Sch, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[23] Sichuan Univ, State Key Lab Biotherapy, Chengdu, Peoples R China

[24] Sun Yat Sen Univ, Affiliated Hosp 1, Inst Precis Med, Guangzhou, Peoples R China

[25] Nanjing Med Univ, Affiliated Huaian Peoples Hosp 1, Dept Resp & Crit Care Med, Huaian 223000, Jiangsu, Peoples R China

来源：

NATURE GENETICS | 2025年 / 57卷 / 04期

关键词：

TRANSCRIPTION FACTORS; COPY NUMBER; R PACKAGE; GENE; TRANSLATION; DISCOVERY; VERSICAN; MUTATIONS; EVOLUTION; HALLMARKS;

D O I：

10.1038/s41588-025-02128-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

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：39

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