Diverse functions of DNA methylation: implications for prostate cancer and beyond

被引:8
作者
Sweet, Thomas J. [1 ]
Ting, Angela H. [1 ]
机构
[1] Cleveland Clin, Lerner Res Inst, Genom Med Inst, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
prostate cancer; DNA methylation; gene expression; MAMMALIAN DNA; RADICAL PROSTATECTOMY; ALTERNATIVE CLEAVAGE; CPG ISLANDS; EXPRESSION; PROMOTER; PROGRESSION; ENHANCERS; GENES; 5-METHYLCYTOSINE;
D O I
10.1530/ERC-16-0306
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Prostate cancer is one of the most common malignancies in men worldwide. Current clinical screening ensures that most prostate cancers are diagnosed while still organ confined, but disease outcome is highly variable. Thus, a better understanding of the molecular features contributing to prostate cancer aggressiveness is being sought. For many cancers, aberrant genome-wide patterns of cytosine DNA methylation in CpG dinucleotides distinguish tumor from normal tissue and contribute to disease progression by altering the transcriptome. In prostate cancer, recent genomic studies identified cancer and high grade-specific differential DNA methylation in gene promoters, gene bodies, gene 3' ends and at distal regulatory elements. Using examples from developmental and disease systems, we will discuss how DNA methylation in each of these genomic contexts can contribute to transcriptome diversity by modulating transcription initiation, alternative transcription start site selection, alternative pre-mRNA splicing and alternative polyadenylation. Alternative transcripts from the same gene often exhibit altered protein-coding potential, translatability, stability and/or localization. All of these can have functional consequences in cells. In future work, it will be important to determine if DNA methylation abnormalities in prostate cancer modify the transcriptome through some or all of these mechanisms and if these DNA methylation-mediated transcriptome alterations impact prostate tumorigenesis and aggressiveness.
引用
收藏
页码:T169 / T178
页数:10
相关论文
共 84 条
  • [1] The Molecular Taxonomy of Primary Prostate Cancer
    Abeshouse, Adam
    Ahn, Jaeil
    Akbani, Rehan
    Ally, Adrian
    Amin, Samirkumar
    Andry, Christopher D.
    Annala, Matti
    Aprikian, Armen
    Armenia, Joshua
    Arora, Arshi
    Auman, J. Todd
    Balasundaram, Miruna
    Balu, Saianand
    Barbieri, Christopher E.
    Bauer, Thomas
    Benz, Christopher C.
    Bergeron, Alain
    Beroukhim, Rameen
    Berrios, Mario
    Bivol, Adrian
    Bodenheimer, Tom
    Boice, Lori
    Bootwalla, Moiz S.
    dos Reis, Rodolfo Borges
    Boutros, Paul C.
    Bowen, Jay
    Bowlby, Reanne
    Boyd, Jeffrey
    Bradley, Robert K.
    Breggia, Anne
    Brimo, Fadi
    Bristow, Christopher A.
    Brooks, Denise
    Broom, Bradley M.
    Bryce, Alan H.
    Bubley, Glenn
    Burks, Eric
    Butterfield, Yaron S. N.
    Button, Michael
    Canes, David
    Carlotti, Carlos G.
    Carlsen, Rebecca
    Carmel, Michel
    Carroll, Peter R.
    Carter, Scott L.
    Cartun, Richard
    Carver, Brett S.
    Chan, June M.
    Chang, Matthew T.
    Chen, Yu
    [J]. CELL, 2015, 163 (04) : 1011 - 1025
  • [2] A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer
    Al Olama, Ali Amin
    Kote-Jarai, Zsofia
    Berndt, Sonja I.
    Conti, David V.
    Schumacher, Fredrick
    Han, Ying
    Benlloch, Sara
    Hazelett, Dennis J.
    Wang, Zhaoming
    Saunders, Ed
    Leongamornlert, Daniel
    Lindstrom, Sara
    Jugurnauth-Little, Sara
    Dadaev, Tokhir
    Tymrakiewicz, Malgorzata
    Stram, Daniel O.
    Rand, Kristin
    Wan, Peggy
    Stram, Alex
    Sheng, Xin
    Pooler, Loreall C.
    Park, Karen
    Xia, Lucy
    Tyrer, Jonathan
    Kolonel, Laurence N.
    Le Marchand, Loic
    Hoover, Robert N.
    Machiela, Mitchell J.
    Yeager, Merideth
    Burdette, Laurie
    Chung, Charles C.
    Hutchinson, Amy
    Yu, Kai
    Goh, Chee
    Ahmed, Mahbubl
    Govindasami, Koveela
    Guy, Michelle
    Tammela, Teuvo L. J.
    Auvinen, Anssi
    Wahlfors, Tlina
    Schleutker, Johanna
    Visakorpi, Tapio
    Leinonen, Katri A.
    Xu, Jianfeng
    Aly, Markus
    Donovan, Jenny
    Travis, Ruth C.
    Key, Tim J.
    Siddiq, Afshan
    Canzian, Federico
    [J]. NATURE GENETICS, 2014, 46 (10) : 1103 - 1109
  • [3] Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer
    Albertsen, PC
    Hanley, JA
    Gleason, DF
    Barry, MJ
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1998, 280 (11): : 975 - 980
  • [4] Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene
    Bachman, KE
    Park, BH
    Rhee, I
    Rajagopalan, H
    Herman, JG
    Baylin, SB
    Kinzler, KW
    Vogelstein, B
    [J]. CANCER CELL, 2003, 3 (01) : 89 - 95
  • [5] DNA methylation and gene silencing in cancer
    Baylin S.B.
    [J]. Nature Clinical Practice Oncology, 2005, 2 (Suppl 1): : S4 - S11
  • [6] CLONING OF A MAMMALIAN DNA METHYLTRANSFERASE
    BESTOR, TH
    [J]. GENE, 1988, 74 (01) : 9 - 12
  • [7] Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer
    Bhasin, Jeffrey M.
    Lee, Byron H.
    Matkin, Lars
    Taylor, Margaret G.
    Hu, Bo
    Xu, Yaomin
    Magi-Galluzzi, Cristina
    Klein, Eric A.
    Ting, Angela H.
    [J]. CELL REPORTS, 2015, 13 (10): : 2135 - 2146
  • [8] Going the distance: A current view of enhancer action
    Blackwood, EM
    Kadonaga, JT
    [J]. SCIENCE, 1998, 281 (5373) : 60 - 63
  • [9] Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes
    Blattler, Adam
    Yao, Lijing
    Witt, Heather
    Guo, Yu
    Nicolet, Charles M.
    Berman, Benjamin P.
    Farnham, Peggy J.
    [J]. GENOME BIOLOGY, 2014, 15 (09): : 469
  • [10] Epigenetic Regulation of Pluripotency and Differentiation
    Boland, Michael J.
    Nazor, Kristopher L.
    Loring, Jeanne F.
    [J]. CIRCULATION RESEARCH, 2014, 115 (02) : 311 - 324