Epigenetics in prostate cancer: Biologic and clinical relevance

Carmen Jerónimo, Patrick J. Bastian, Anders Bjartell, Giuseppina M. Carbone, James W F Catto, Susan J. Clark, Rui Henrique, William G Nelson, Shahrokh F. Shariat

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)753-766
Number of pages14
JournalEuropean Urology
Volume60
Issue number4
DOIs
StatePublished - Oct 2011

Fingerprint

Epigenomics
Prostatic Neoplasms
DNA Methylation
Histone Code
MicroRNAs
Gene Expression
Chromatin Assembly and Disassembly
Genomic Instability
Gene Fusion
Androgen Receptors
PubMed
Histones
Publications
Prostate
Carcinogenesis
Biomarkers
Apoptosis
Enzymes
Genes

Keywords

  • Detection and prognosis
  • DNA methylation
  • Epigenetics
  • Histone modifications
  • MicroRNAs
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

Jerónimo, C., Bastian, P. J., Bjartell, A., Carbone, G. M., Catto, J. W. F., Clark, S. J., ... Shariat, S. F. (2011). Epigenetics in prostate cancer: Biologic and clinical relevance. European Urology, 60(4), 753-766. https://doi.org/10.1016/j.eururo.2011.06.035

Epigenetics in prostate cancer : Biologic and clinical relevance. / Jerónimo, Carmen; Bastian, Patrick J.; Bjartell, Anders; Carbone, Giuseppina M.; Catto, James W F; Clark, Susan J.; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F.

In: European Urology, Vol. 60, No. 4, 10.2011, p. 753-766.

Research output: Contribution to journalArticle

Jerónimo, C, Bastian, PJ, Bjartell, A, Carbone, GM, Catto, JWF, Clark, SJ, Henrique, R, Nelson, WG & Shariat, SF 2011, 'Epigenetics in prostate cancer: Biologic and clinical relevance', European Urology, vol. 60, no. 4, pp. 753-766. https://doi.org/10.1016/j.eururo.2011.06.035
Jerónimo C, Bastian PJ, Bjartell A, Carbone GM, Catto JWF, Clark SJ et al. Epigenetics in prostate cancer: Biologic and clinical relevance. European Urology. 2011 Oct;60(4):753-766. https://doi.org/10.1016/j.eururo.2011.06.035
Jerónimo, Carmen ; Bastian, Patrick J. ; Bjartell, Anders ; Carbone, Giuseppina M. ; Catto, James W F ; Clark, Susan J. ; Henrique, Rui ; Nelson, William G ; Shariat, Shahrokh F. / Epigenetics in prostate cancer : Biologic and clinical relevance. In: European Urology. 2011 ; Vol. 60, No. 4. pp. 753-766.
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