QuantitativeRARβ2Hypermethylation

Abstract

Retinoic acid receptor ␤2 (RAR␤2) is a tumor suppressor gene frequently hypermethylated in several human neoplasms. To further characterize this epigenetic alteration in prostate cancer progression, we examined tumor tissue from 118 patients with prostate carcinoma (PCa), 38 paired highgrade prostatic intraepithelial neoplasias (HGPIN), and nonneoplastic prostate tissue from 30 patients with benign prostate hyperplasia (BPH), using quantitative methylation-specific PCR. We found RAR␤2 hypermethylation in 97.5% of PCa, 94.7% of HGPIN, and 23.3% of BPH. Methylation levels were significantly higher in PCa compared with HGPIN and BPH (P < 0.00001). By establishing an empiric cutoff value, we were able to discriminate between neoplastic and non-neoplastic tissue, with 94.9% sensitivity and 100% specificity. Moreover, RAR␤2 methylation levels correlated with higher pathological stage (r ‫؍‬ 0.30, P ‫؍‬ 0.0009). This quantitative assay represents a novel and promising molecular marker that may augment current approaches for prostate cancer detection.

Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

“…However, unlike detection of prostate cancer DNA using tests for methylation marks, DNA methylation biomarkers for prostate cancer prognosis are still limited. Methylation marks for EDNRB, RARb, RASSF1a, ERb, and TIG1 may be suitable for this unmet need as each has been correlated with known prognostic factors for primary prostate cancer, such as tumor stage and/or Gleason grade (22)(23)(24)(25)59). Indeed in 1 study, PTGS2 methylation marks in the localized prostate cancer predicted prostate cancer recurrence after radical prostatectomy, independently of tumor stage and Gleason grade (60).…”

“…Notably hypermethylation of the glutathione S-transferase P1 (GSTP1) gene occurs in approximately 90% of all prostate cancers and is an early event, with DNA methylation lesions common in prostate intraepithelial neoplasia, making this gene a useful marker for early prostate cancer detection (17,18). In addition to GSTP1, more than 40 genes have been reported to be targets of epigenetic gene silencing in prostate cancers (19) including adenomatosis polyposis coli (APC), Ras association domain family 1A (RASSF1A), prostaglandinendoperoxidase synthase 2 (PTGS2), multidrug resistance gene 1 (MDR1), retinoic acid receptor beta 2 (RARb2), tazarotene-induced gene-1 (TIG1), and oestrogen receptor-beta (ER-b), which have also been shown to be involved in tumor initiation and progression and have been correlated with clinicopathologic parameters (20)(21)(22)(23)(24)(25). A number of groups have also attempted to use combinations of genes to develop improved methylation-based tests for disease progression (26)(27)(28); however, no current epigenetic biomarker can predict disease aggressiveness or survival better than Gleason grade and serum PSA tests.…”

Application of histone modification in the risk prediction of the biochemical recurrence after radical prostatectomy

“…During the prostate carcinogenesis, epigenetic changes are so frequent that they allow the discrimination between the normal and neoplastic tissues with a specificity of up to 100% [29,30], some histone modifications are associated with the increased risk of low-grade prostate cancer recurrence [20]. However, the relationship between global histone modification and the prostate cancer progression remains elusive [31].…”

Subtypes of White Blood Cells in Patients with Prostate Cancer or Benign Prostatic Hyperplasia and Healthy Individuals

“…Today, clinicians have been become interested in novel direct or indirect diagnostic methods to overcome such problems. Thus, several molecular, biological and serological studies have been undertaken (Jeromino et al, 2004;Beer et al, 2008;Mengus et al, 2011).…”