Abstract

Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention.

Keywords

EpigeneticsProstate cancerTMPRSS2EZH2BiologyHistoneCancerHistone deacetylaseCancer researchDNA methylationProstateEpigenomicsBioinformaticsGeneticsDiseaseMedicineInternal medicineGene expressionGene

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Publication Info

Year
2008
Type
review
Volume
100
Issue
2
Pages
240-245
Citations
105
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Christopher S. Cooper, Christopher S. Foster (2008). Concepts of epigenetics in prostate cancer development. British Journal of Cancer , 100 (2) , 240-245. https://doi.org/10.1038/sj.bjc.6604771

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DOI
10.1038/sj.bjc.6604771