title: Epigenetics in prostate cancer: biologic and clinical relevance.
abstract: BACKGROUND
  Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence.
  
  
  OBJECTIVE
  To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge.
  
  
  METHODS
  PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications.
  
  
  RESULTS
  Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance.
  
  
  CONCLUSIONS
  Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic.
authors: Cancer Epigenetics Group-Research Center, Department of Genetics, Portuguese Oncology Institute-Porto, Portugal. carmenjeronimo@ipoporto.min-saude.pt
authors: Carmen
authors: C
authors: Jerónimo
authors: Patrick J
authors: PJ
authors: Bastian
authors: Anders
authors: A
authors: Bjartell
authors: Giuseppina M
authors: GM
authors: Carbone
authors: James W F
authors: JW
authors: Catto
authors: Susan J
authors: SJ
authors: Clark
authors: Rui
authors: R
authors: Henrique
authors: William G
authors: WG
authors: Nelson
authors: Shahrokh F
authors: SF
authors: Shariat
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D035683:MicroRNAs; D011944:Receptors, Androgen; D004248:DNA (Cytosine-5-)-Methyltransferases