Editing Prostate Cancer: Epidemiology and Pathogenesis (section)

== Molecular Genetics ==

* Biologic functions of known prostate cancer susceptibility genes include:
*# Control of the inflammatory response
*# Homeobox genes
*# DNA repair mechanisms
*# Susceptibility to infection
* '''<span style="color:#ff0000">Most common gene fusion identified in localized prostate cancer involves TMPRSS2</span>''' or other promoters (SLC45A3, HERPUD1, or NDRG) '''<span style="color:#ff0000">fused to ERG (ETS-related gene)</span>'''
** '''The TMPRSS2 gene is prostate specific, and is expressed in both benign and malignant prostatic epithelium;'''
** '''TMPRSS2:ERG fusion gene is detected in ≈50% of prostate cancers'''
** '''TMPRSS2-ERG fusion gene is present in prostate stem cells'''
** '''TMPRSS2 expression has been shown to be induced by androgens'''
** '''TRMPSS2-related gene fusions are highly specific for the presence of prostate cancer'''
* Most common point mutations in prostate cancer are mutations in SPOP, which encodes a subunit of ubiquitin ligase
* Current evidence suggests that most prostate cancer is polygenic in origin. GWAS studies have identified more than 70 risk alleles and chromosomal loci, many of which occur in non-coding areas of the genome. A variety of genes implicated in prostate cancer initiation and progression include
** Hypermethylation of
*** Hormonal response genes (ERαA, ERβ, and RARβ)
*** Genes controlling the cell cycle (CyclinD2 and 14-3-3σ)
*** Tumor cell invasion/tumor architecture genes (CD44)
*** DNA repair genes (GSTpi, GPX3, and GSTM1)
*** Tumor suppressor genes (APC, RASSF1α, DKK3, p16INK4?−α, E-cadherin, and p57WAF1)
*** Signal transduction genes (EDNRB and SFRP1)
*** Inflammatory response genes (PTGS/COX2)
** Hypomethylation of CAGE, HPSE, and PLAU
** Histone hypoacetylation of CAR, CPA3, RARB, and VDR
** Histone methylation of GSTP1 and PSA
* Epigenetic mechanisms active in prostate cancer include:
*# Chromatin remodeling
*# Promoter hypomethylation and hypermethylation
*# MicroRNAs that lead to gene silencing
*# Long non-coding RNAs