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Epigenetics in Prostate Cancer: Biologic and Clinical Relevance

Jeronimo, Carmen; Bastian, Patrick J.; Bjartell, Anders LU ; Carbone, Giuseppina M.; Catto, James W. F.; Clark, Susan J.; Henrique, Rui; Nelson, William G. and Shariat, Shahrokh F. (2011) In European Urology 60(4). p.753-766
Abstract
Context: 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. Evidence acquisition: 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. Evidence synthesis: Aberrant DNA... (More)
Context: 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. Evidence acquisition: 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. Evidence synthesis: 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. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Prostate cancer, Epigenetics, DNA methylation, Histone modifications, MicroRNAs, Detection and prognosis
in
European Urology
volume
60
issue
4
pages
753 - 766
publisher
Elsevier
external identifiers
  • wos:000294304100029
  • scopus:80052260149
ISSN
1873-7560
DOI
10.1016/j.eururo.2011.06.035
language
English
LU publication?
yes
id
094003be-8ed7-4ce0-8425-456d6be401dc (old id 2187012)
date added to LUP
2011-11-01 07:53:09
date last changed
2017-10-01 04:05:09
@article{094003be-8ed7-4ce0-8425-456d6be401dc,
  abstract     = {Context: 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. Evidence acquisition: 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. Evidence synthesis: 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. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.},
  author       = {Jeronimo, Carmen and Bastian, Patrick J. and Bjartell, Anders and Carbone, Giuseppina M. and Catto, James W. F. and Clark, Susan J. and Henrique, Rui and Nelson, William G. and Shariat, Shahrokh F.},
  issn         = {1873-7560},
  keyword      = {Prostate cancer,Epigenetics,DNA methylation,Histone modifications,MicroRNAs,Detection and prognosis},
  language     = {eng},
  number       = {4},
  pages        = {753--766},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Epigenetics in Prostate Cancer: Biologic and Clinical Relevance},
  url          = {http://dx.doi.org/10.1016/j.eururo.2011.06.035},
  volume       = {60},
  year         = {2011},
}