Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome?

Brothman, Arthur R.; Swanson, Gregory P.; Maxwell, Teresa; Cui, Jiang; Murphy, Kelley J.; Herrick, Jennifer S.; Speights, V. O.; Isaac, Jorge; Rohr, L. Ralph

doi:10.1016/j.cancergencyto.2004.04.004

Cited by 82 publications

(67 citation statements)

References 17 publications

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“…The present work described the immunohistochemical method set up to visualize and quantify the 5-MC signal in paraffin embedded tissue sections. The results were consistent with a previous report, which showed that most primary prostate cancer exhibited a global decrease in methylation compared with normal tissues with a similar immunohistochemical method [17]. This further suggests that immunohistochemistry with 5-MC antibody is a reproducible method in analysis of the alterations of 5-MC in prostate cancers.…”

Section: Discussionsupporting

confidence: 94%

Evaluation of global DNA hypomethylation in human prostate cancer and prostatic intraepithelial neoplasm tissues by immunohistochemistry

Yang¹,

Sun²,

Lin³

et al. 2013

Urologic Oncology: Seminars and Original Investigations

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Section: Discussionsupporting

confidence: 94%

Evaluation of global DNA hypomethylation in human prostate cancer and prostatic intraepithelial neoplasm tissues by immunohistochemistry

Yang¹,

Sun²,

Lin³

et al. 2013

Urologic Oncology: Seminars and Original Investigations

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“…DNA hypomethylation may be detected early in carcinogenesis, however, it is also often associated with cancer progression (18). Hypomethylation may promote carcinogenesis by causing an increase in DNA recombination, and via direct and indirect effects on protein expression (19). Repeated DNA sequences that are frequently hypomethylated in cancer tissue may act as tumor markers for cancer diagnosis and prognosis (17).…”

Section: Discussionmentioning

confidence: 99%

Expression of CC chemokine receptor 5 in clear cell renal cell carcinoma and its clinical significance

et al. 2015

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Abstract. DNA hypomethylation was the initial epigenetic abnormality recognized in human malignancy. In the present study, the GoldenGate high-throughput genotyping assay was adapted to determine the methylation state of 1,505 specific CpG sites in 807 cancer-related genes. The methylation results revealed that CC chemokine receptor 5 (CCR5) was hypomethylated (mean β-value difference, -0.21) in clear cell renal cell carcinoma (CCRCC) tissue. Tissue samples from 61 CCRCC cases were used for immunohistochemical staining, and patients with low CCR5 expression (n=44) were compared with those with high CCR5 expression (n=17). Tumor (T) stage was significantly lower in the low expression group compared with the high expression group (P=0.047). The Fuhrman grade of patients in the low expression group was significantly lower than that of patients in the high expression group (P=0.044). Whilst the node (N) and metastasis (M) stages of the CCR5 low expression group appeared to be lower compared with those of the CCR5 high expression group; this difference was not statistically significant (N stage, P=0.632; M stage, P=0.896). Additionally, patients in the low expression group had lower risks of postoperative tumor recurrence (P=0.110) and mortality from CCRCC (P=0.159) compared with those in the high expression group, however, this was also without statistical significance. The results indicate that CCR5 hypomethylation is associated with cancer tissue to a greater extent than normal tissue. Although the biological function of CCR5 in CCRCC remains to be established, low CCR5 expression is associated with low T stage and low Fuhrman grade in these patients.

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“…In mice carrying a hypomorphic Dnmt1, a genome-wide hypomethylation was observed in addition to animals developing aggressive T-cell lymphomas at age of 4-8 months, indicating that DNA hypomethylation plays a causal role in tumor formation (Gaudet et al, 2003). Although global hypomethylation was suggested to be a common event in prostate cancer (Brothman et al, 2005), very little information exists regarding the target genes regulated by hypomethylation in prostate cancer (Ogishima et al, 2005;Tokizane et al, 2005). In this study, we identify upregulation of WNT5A, S100P and cysteine-rich protein 1 (CRIP1) in prostate cancers to be associated with 5 0 untranslated region (UTR) hypomethylation.…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer

et al. 2007

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Oligoarray analysis of a matched pair of prostate cancer and normal cell lines derived from the same radical prostatectomy specimen identified 113 candidate hypomethylated genes that were overexpressed in the cancer cells and contained CpG islands. Hypomethylation of wingless-related MMTV integration site 5A (WNT5A), S100 calcium-binding protein P (S100P) and cysteine-rich protein 1(CRIP1) was confirmed in the cancer cells by bisulfite sequencing. Treatment of the corresponding normal prostate epithelial cells 1542-NPTX with the DNA methyltransferase inhibitor 5-Aza-2 0 -deoxycytidine (5-aza-CdR) induced higher levels of mRNA expression and partial loss of methylation on these genes. Primary prostate cancers were tested using methylation-specific polymerase chain reaction. WNT5A was hypomethylated in 11/17 (65%) tumors, S100P in 8/16 (50%) and CRIP1 in 13/20 (65%). Bisulfite sequencing of a section of the 5 0 untranslated region (UTR) of WNT5A revealed that three CpG sites (15, 24 and 35) were consistently methylated (93%) in the normal cell line and normal tissues, but not in the prostate cancer cell line and eight primary prostate cancers. Multiple putative binding sites for the transcription factors SP1 and AP-2 were found adjacent to CpG sites 15 and 24. A putative c-Myb binding site was located within the CpG site 35. Anti-c-Myb antibody co-precipitation with WNT5A was methylation-sensitive in 1542-NPTX cells. It is likely that an epigenetic mechanism regulates WNT5A expression in prostate cancer.

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Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome?

Cited by 82 publications

References 17 publications

Evaluation of global DNA hypomethylation in human prostate cancer and prostatic intraepithelial neoplasm tissues by immunohistochemistry

Evaluation of global DNA hypomethylation in human prostate cancer and prostatic intraepithelial neoplasm tissues by immunohistochemistry

Expression of CC chemokine receptor 5 in clear cell renal cell carcinoma and its clinical significance

Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer

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