Epigenetic Mechanisms: Histone Acetylation, DNA Methylation, miRNA, Chromatin Modifiers

In prostate cancer DNA methylation have been recorded as one of the main epigenetic event. More than 50 genes, in fact, have been found hypermethy- lated in prostate cancer (Li et al., Biochim Biophys Acta 1704:87-102, 2004; Nelson et al., Front Biosci 12:4254-4266, 2007). However, only a small number of genes, e.g. RASSF1A, RARB2, APC, and GSTP1 (Florl et al., Br J Cancer 91:985-994, 2004) or GSTP1, APC and MDR1 (Enokida et al., Clin Cancer Res 11:6582- 6588, 2005) can help to discriminate between benign and cancerous changes in the prostate, by hypermethylation assay. The assays for genes hypermethylated in a fraction of the cases may help to distinguish different subgroups of prostate cancer, even if the low sensitivity of the assay is mostly dependent on the amount of DNA obtained by the primary sample (biopsy, serum, urine). Then, the reliability of this tests, unfortunately, is still low (Li et al., Biochim Biophys Acta 1704:87-102, 2004). Hypermethylation at some genes may be dynamic during tumor progression, as in the case of the ESR2 gene encoding the estrogen receptor (Zhu et al. 2004). Otherwise, methylation at some genes is varying, affecting the methylation-specific PCR assays. Hypermethylation of genes like GSTP1, detected in high percentage of prostate cancers, occur at an early stage of cancer development and is detected in the best-established precursor lesion of prostate cancer, high-grade prostatic in- traepithelial neoplasia (HG-PIN). The specificity of genes methylation in carcinoma is confirmed by the weak methylation of the same genes in morphologically benign adjacent areas. A "field effect" which may promote the onset of carcinomas has also been reported (Florl et al. 2004; Aitchinson et al. 2007). IIn prostate cancer DNA methylation have been recorded as one of the main epigenetic event. More than 50 genes, in fact, have been found hypermethy- lated in prostate cancer (Li et al., Biochim Biophys Acta 1704:87-102, 2004; Nelson et al., Front Biosci 12:4254-4266, 2007). However, only a small number of genes, e.g. RASSF1A, RARB2, APC, and GSTP1 (Florl et al., Br J Cancer 91:985-994, 2004) or GSTP1, APC and MDR1 (Enokida et al., Clin Cancer Res 11:6582- 6588, 2005) can help to discriminate between benign and cancerous changes in the prostate, by hypermethylation assay. The assays for genes hypermethylated in a fraction of the cases may help to distinguish different subgroups of prostate cancer, even if the low sensitivity of the assay is mostly dependent on the amount of DNA obtained by the primary sample (biopsy, serum, urine). Then, the reliability of this tests, unfortunately, is still low (Li et al., Biochim Biophys Acta 1704:87-102, 2004). Hypermethylation at some genes may be dynamic during tumor progression, as in the case of the ESR2 gene encoding the estrogen receptor (Zhu et al. 2004). Otherwise, methylation at some genes is varying, affecting the methylation-specific PCR assays. Hypermethylation of genes like GSTP1, detected in high percentage of prostate cancers, occur at an early stage of cancer development and is detected in the best-established precursor lesion of prostate cancer, high-grade prostatic in- traepithelial neoplasia (HG-PIN). The specificity of genes methylation in carcinoma is confirmed by the weak methylation of the same genes in morphologically benign adjacent areas. A "field effect" which may promote the onset of carcinomas has also been reported (Florl et al. 2004; Aitchinson et al. 2007). IIn prostate cancer DNA methylation have been recorded as one of the main epigenetic event. More than 50 genes, in fact, have been found hypermethy- lated in prostate cancer (Li et al., Biochim Biophys Acta 1704:87-102, 2004; Nelson et al., Front Biosci 12:4254-4266, 2007). However, only a sm