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Page 344 Jones et al. J Transl Genet Genom 2021;5:341-56 https://dx.doi.org/10.20517/jtgg.2021.19

Figure 1. Epigenetics in PCa. Diagram illustrating how epigenetic changes related to prostate cancer and which inhibitors are in current
studies. ASF1A: Anti-silencing function 1A hisotne chaperone; CAF-1: chromatin assembly factor 1; SAFB1: scaffold attachment factor B;
DNMT: DNA methyltransferase; EZH2: enhancer of zeste 2 polycomb repressive complex 2 subunit; CBP: CREB-binding protein; BRD4:
bromodomain containing 4; BET: bromodomain and extra terminal domain; HDAC: histone deacetylases; KDM1A: lysine demethylase
1A; CM-272: 6-methoxy-2-(5-methylfuran-2-yl)-N-(1-methylpiperidin-4-yl)-7-(3-(pyrrolidin-1-yl)propoxy)quinolin-4-amine; UNC-
06358: 2-cyclohexyl-6-methoxy-N-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine; JQ1: (S)-tert-butyl 2-
(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; TCP: tranylcypromine; ORY-
1001: idademstat; IMG-7289: bomedemstat HCL; INCB059872: 1-((4-(methoxymethyl)-4-((((1R,2S)-2-
phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)cyclobutane-1-carboxylic acid compound with 4-methylbenzenesulfonic acid
(1:2); CC-90011: besylate; ORY-2001: vafidemstat.

hypermethylation cluster for prognostic purposes . In another study analyzing 84 prostatic tumor tissues
[17]
with low and intermediate grade PCa, DNA hypermethylation was associated with poorer prognosis and
prostate-specific antigen (PSA) recurrence following prostatectomy . Comparing DNA methylation in
[18]
PCa tissues to benign prostatic hyperplasia tissues revealed a higher occurrence of hypermethylation in a
group of genes, suggesting a role for these signatures in the diagnostic and prognostic setting of PCa . The
[18]
hypomethylation of MYC’s exon3 is not associated with changes in its expression; however, it was
associated with a more aggressive phenotype in the examined cohort . In another study and contrary to
[19]
the established consensus, a group of hypermethylated genes in PCa tumors was associated with increased
[20]
gene expression . In an Iranian study, 35 prostate tumor samples were examined before and after hormone
therapy treatment. Treatment with bicalutamide-based drugs for three months induced a significant
decrease in the expression of DNMT3A and significant increases in the expression of DNMT3B and two
[21]
[22]
well-established methylated genes, GSTP1 and RASSF1 . Gravina et al. showed that treatment with
bicalutamide induced an increase in DNMT activity in PCa that correlated with an increased expression of
DNMT3A and DNMT3B. These observations warrant further investigation to understand better the
regulation of DNA methylation patterns in PCa, their effects on disease progression, and treatment
decisions moving forward.