CpG Island Hypermethylation at Multiple Gene Sites in Diagnosis and Prognosis of Prostate Cancer

Ellinger, Jörg; Bastian, Patrick J.; Jurgan, Thomas; Biermann, Katharina; Kahl, Philip; Heukamp, Lukas C.; Wernert, Nicolas; Müller, Stefan; Ruecker, Alexander von

doi:10.1016/j.urology.2007.09.056

Cited by 118 publications

(98 citation statements)

References 24 publications

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“…Possibly multiple analysis of methylation in more than one imprinted genes such as KCNQ1, LIT1, TSSC5, GRB10 and MEG3 may improve clinical significance. Studies presented by Ellinger et al (27) showed that hypermethylation at a single gene locus did not correlate with any clinicopathological variables. In contrast, hypermethylation at two genes (e.g., APC and TIG1, APC and GSTP1, APC and PTGS2, APC or MDR, GSTP1 or PTGS2) correlated significantly with the pathologic stage and/or Gleason score (p=0.033 to 0.045).…”

Section: Discussionmentioning

confidence: 93%

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Paradowska

Fenic²,

Konrad³

et al. 2009

Int J Oncol

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Abstract. Expression of the imprinted genes insulin-like growth factor 2 (IGF2) and H19 depends on the methylation pattern of their common imprinting control region (ICR) located on chromosome 11p15. As the somatic imprinting pattern may be lost during tumorigenesis due to epigenetic alterations, in the present study, we analyzed the DNA methylation and histone modifications in the differentially methylated region (DMR) of IGF2/H19 in benign prostate hyperplasia (BPH) and prostate carcinoma (PCa). Sodium bisulfite sequencing was performed on frozen tissue collected after radical prostatectomy. Thirty tumors and 17 noncancerous tissue samples were analyzed. Histological diagnosis was, in addition, confirmed by amplification of the epithelial tumor marker ·-methylacyl coenzyme-A racemase. Chromatin immunoprecipitation assay (ChIP) was carried out on sonificated chromatin from fresh tissue samples from 10 PCa, 10 BPH using antibodies against trimethyl histone H3K9, dimethyl histone H3K9, trimethyl H3K27 and acetyl H3K9. The methylation pattern of 17 CpGs within 227 bp of the H19 fragment was characterized from each DNA sample. All (BPH) samples demonstrated >80% methylation of CpGs. In contrast, we found 41% of CpGs methylated in 9 out of 30 PCa specimens. We observed statistically significant differences in the methylation state between PCa and BPH groups, especially in the DMR of H19 (p<0.0001) and in the ICR (p=0.0034), which corresponds to CTCF binding domain. ChIP assay revealed that dimethyl H3K9 is associated with the ICR of IGF2/H19 in BPH, but not in PCa (p<0.0001). Our data demonstrate that DNA methylation and histone methylation analysis of the ICR within the DMR of IGF2/H19 provides important insights into early steps of carcinogenesis and, therefore, may contribute to improving diagnosis of PCa.

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Section: Discussionmentioning

confidence: 93%

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Paradowska

Fenic²,

Konrad³

et al. 2009

Int J Oncol

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“…Our search strategy and application of the inclusion/exclusion criteria resulted in a total of 19 articles that were included in the systematic review. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] A description of the included studies is given in Tables 1 and 2. The following data were recorded for each study: author's name, year of publication, sample forms, method, 5 0 -3 0 primers (forward and reverse, respectively), amplicon size (bp) and annealing temperature (1C), country, race, cancer clinical classification, PSA, Gleason score, type of cases and controls, type of PCR method and other relevant characteristics of the study population.…”

Section: Study Selectionmentioning

confidence: 99%

“…[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] Finally, 19 studies met the inclusion criteria and were included. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Among these 19 studies, 5 involved body fluid (blood, urine and so on) [11][12][13][14][15] and the remaining 14 articles involved sample tissues. [16][17][18][19][20][21][22][23][24][25][26][27]…”

Section: Characteristicsmentioning

confidence: 99%

“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Among these 19 studies, 5 involved body fluid (blood, urine and so on) [11][12][13][14][15] and the remaining 14 articles involved sample tissues. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] Ten studies used quantitative real-time methylation-specific PCR (QMSP) to detect APC methylation, 11,13,14,18,19,[21][22][23]25,26 seven were conducted using the method of methylation-specific PCR (MSP), 12,15,...…”

Section: Characteristicsmentioning

confidence: 99%

“…Finally, one study 13 and four articles 19,20,22,26 in the fluid and tissue subgroups, respectively, with different samples. The pooled specificity (0.90, 95% CI: 0.77-0.96) and pooled sensitivity (0.78, 95% CI: 0.59-0.90) were similar to the previous results.…”

Section: Characteristicsmentioning

confidence: 99%

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APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis

Chen

et al. 2013

Eur J Hum Genet

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Prostate cancer (PCa) is a worldwide disease that affects a large number of males. Although prostate-specific antigen (PSA) screening is used, the specificity is limited. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for PCa detection in body fluids and tissues. Combining search results from PubMed and Embase, 19 studies were included, 5 involving body fluids and 14 involving prostate tissue, with 2344 subjects. In body fluid subgroups, the pooled sensitivity and specificity was 0.53 (95% confidence interval (CI): 0.28-0.78) and 0.92 (95% CI: 0.86-0.95), respectively. From tissue studies, the results presented as 0.84 (95% CI: 0.70-0.92) and 0.91 (95% CI: 0.77-0.97). To confirm the results, we conducted a further analysis by removing studies which introduced high heterogeneity due to the type of cases and controls. The same degree of sensitivity and specificity was presented in two subgroups (urine: sensitivity 0.46, 95% CI: 0.39-0.53; specificity 0.87, 95% CI: 0.64-0.96; tissue: sensitivity 0.87, 95% CI: 0.72-0.94; specificity 0.89, 95% CI: 0.68-0.97). In addition, analysis of the interaction between APC methylation and PCa showed strong association in the whole data set (odds ratio (OR) ¼ 24.91, 95% CI: 12.86-48.24, I 2 ¼ 72.5%). Pooling the same two main subgroups (tissue/fluid) gave a pooled OR of 33.54 (95% CI: 14.88-75.59; I 2 ¼ 70.7%) and 8.20 (95% CI: 2.84-23.74, I 2 ¼ 64.2%), respectively. From this study, the results suggest that APC promoter methylation may be the potential testing for PCa diagnosis and provide a new viewpoint in the treatment of PCa.

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Biomolecular markers of outcome prediction in prostate cancer

Lopergolo¹,

Zaffaroni

2009

Cancer

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Prostate cancer has a variable clinical outcome and, therefore, there is a clear need for novel molecular markers that are specifically associated with biologically aggressive disease to improve staging and prognostication and also to provide mechanistic information to facilitate treatment selection. Different candidate biomarkers have been identified that are linked to patient prognosis and/or response to specific treatments. Such molecules are involved in diverse cellular processes (including cell cycle regulation, cell death and apoptosis, signal transduction, cell adhesion, and angiogenesis) within which aberrant activity of several regulatory pathways has been seen in prostate cancer. Although the number of molecular markers continues to grow, mainly because of the advent of high-throughput methods, more work needs to be done to develop uniform standards for their characterization to enable comparison of markers across studies. Moreover, a rate-limiting step in the development of molecular markers is large-scale clinical assess-

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CpG Island Hypermethylation at Multiple Gene Sites in Diagnosis and Prognosis of Prostate Cancer

Cited by 118 publications

References 24 publications

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

Aberrant epigenetic modifications in the CTCF binding domain of the IGF2/H19 gene in prostate cancer compared with benign prostate hyperplasia

APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis

Biomolecular markers of outcome prediction in prostate cancer

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