DNA methylation and prostate cancer
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PROVIDER: PRJNA578778 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation and prostate cancer
| PRJNA578779 | ENA
Project description:The aim of this study was to analyze critically the potential usefulness of selected DNA methylation biomarkers in supporting conventional histological diagnostic tests for PCa. The selection of potential biomarkers was conducted by microarray profiling of DNA methylation on prostate tissues extracted from the gland after total radical prostatectomy. DNA methylation profiles of 16 prostate samples without carcinoma and 16 matched pairs of samples with and without cancer cells isolated from prostates containing prostate carcinoma
2014-07-01 | E-GEOD-55598 | biostudies-arrayexpress
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in prostate tissues (n=17) and cells (n=2) from fifty nanograms of genomic DNA using Methylplex-Next Generation Sequencing (M-NGS). A Hidden Markov Model (HMM)-based algorithm previously used for Chip-Seq data analysis(http://www.sph.umich.edu/csg/qin/HPeak) was used to locate peaks from mapped reads obtained in each sequencing run. The total methylation events in intergenic/intronic regions between benign adjacent and cancer tissues were comparable. While approximately 20% of all CpG islands (CGIs) (68,508) were methylated in tissues, promoter CGI methylation gradually increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues. We found distinct patterns in promoter methylation around transcription start sites, where methylation occurred directly on the CGIs, flanking regions and on CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific and several previously studied targets were among them. A novel cancer specific DMR in WFDC2 promoter showed 77% methylation in cancer (17/22), 100% methylation in transformed prostate cell lines (6/6), none in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested a role for DNA methylation in alternate transcription start site utilization. While methylated promoters containing CGIs had mutually exclusive H3K4me3 modification, the histone mark was absent in CGI sparse promoters. Finally, we observed difference in methylation of LINE-1 elements between transcription factor ERG positive and negative cancers. The comprehensive methylome map presented here will further our understanding of epigenetic regulation of the prostate cancer genome. We mapped the global DNA methylation patterns in prostate tissues (n=17; data not available in GEO - being deposited in dbGaP for controlled access) and cells (n=2) from fifty nanograms of genomic DNA using Methylplex-Next Generation Sequencing (M-NGS). For replicate analysis in cell lines, a total of 4 runs were completed for PrEC prostate normal cell line, and 5 runs were completed for LNCaP prostate cancer cell line. For tissue samples, 2 benign prostate samples were ran twice on illumina next generation sequencing platform to access overall repeatability of M-NGS.
2011-05-09 | E-GEOD-27618 | biostudies-arrayexpress
Project description:A major challenge in the clinical management of prostate cancer is the inability to definitively diagnose indolent versus aggressive cases. Contributing to this challenge is a lack of basic science understanding of the molecular basis behind aggressiveness subtypes in prostate cancer. DNA methylation is the epigenetic addition of a methyl group to the DNA base cytosine and has been found to regulate cell proliferation and environmental adaptation. We hypothesized that DNA methylation changes are a mechanism by which an aggressive cancer attains phenotypes that distinguish it from indolent cases via disruption of regulatory networks. This hypothesis was tested by comparing DNA methylation between benign prostate and both low grade (Gleason score 6) and high grade (Gleason score 8 to 10) groups. Methylome-wide next generation sequencing was performed on formalin-fixed paraffin embedded (FFPE) samples from radical prostatectomy cases using MBD-isolated genome sequencing (MiGS). This technique uses a DNA methylation binding protein (MBD) to purify fragments from a genomic library with a high level of CpG DNA methylation. These fragments were then sequenced via next generation sequencing, the reads were aligned to a reference genome, and then the reads were counted within non-overlapping 50bp windows genome wide. Statistical analysis was then performed on these windowed counts to produce differentially methylated regions (DMRs). MBD-isolated Genome Sequencing (MiGS) for groups of benign prostate (from cystoprostatectomy), low grade prostate cancer (from radical prostatectomy with Gleason Score 6), and high grade prostate cancer (from radical prostatectomy with Gleason Scores 8 to 10) in both European Americans and African Americans
2015-11-01 | E-GEOD-66505 | biostudies-arrayexpress
Project description:DNA methylation analysis of paired prostate tumor and noncancerous tissues was perform in order to identify potential DNA methylation biomarkers for prostate cancer diagnostics and prognosis. Based on comparison of tumors versus noncancerous tissues and cases with and without biochemical disease recurrence (BCR), several gene targets were selected for more detailed analysis. Differences in methylation were further confirmed by means of methylation-specific PCR and significantly correlated with gene expression. Survival analysis indicated various combinations of DNA methylation biomarkers as significant prognosticaters of time to BCR, therefore, showing their potential clinical significance.
2017-04-30 | GSE89243 | GEO
Project description:Genome wide DNA methylation profiling of androgen-sensitive and –refractory prostate cancer cells. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles across approximately 480.000 CpGs in Prostate cancer cell lines showing different sensitivity to hormonal treatments. Samples included the androgen receptor negative cell lines PC3 and DU145, the androgen sensitive cell line LNCaP and the LNCaP abl cell line expressing androgen receptor but refractory prostate cancer cell line to hormonal treatments.
2023-12-31 | GSE217962 | GEO
Project description:Microarray-based DNA methylation and gene expression profiling was carried out using a panel of prostate cancer cell lines (LNCaP-FGC, DU-145, and PC-3) and the control normal prostate RWPE1 cell line. The identification of prostate cancer-specific methylation markers was based on the following criteria: a difference in DNA methylation level (β) of at least 0.5, and at least a 2-fold difference in expression level between cancer and control cells. Using highly stringent selection criteria, we identified novel hypermethylated genes whose expression was silenced in prostate cancer cells.
2011-07-25 | GSE23388 | GEO
Project description:DNA methylation profiling of normal prostates from organ donors and prostate cancer metastases from a rapid autopsy cohort of lethal metastatic prostate cancer Metastases from prostate cancer patients. Normal prostate samples from organ donors
2013-02-04 | E-GEOD-38240 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of normal and tumor prostate samples, as well as cultured primary prostate cells overexpressing DNA Methyltransferases (DNMTs) and EZH2 Candidate gene based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer. However, DNA methylation profiles have not been compared on a large scale between prostate tumor and normal prostate, and the mechanisms behind these alterations are unknown. In this study, we quantitatively profiled 95 primary prostate tumors and 86 healthy prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform. A 2-class Significance Analysis of this dataset revealed 5,912 CpG sites with increased DNA methylation and 2,151 CpG sites with decreased DNA methylation in tumors (FDR < 0.8%). Prediction Analysis of this dataset identified 87 CpGs that are the most predictive diagnostic methylation biomarkers of prostate cancer. By integrating available clinical follow-up data, we also identified 69 prognostic DNA methylation alterations that correlate with biochemical recurrence of the tumor. To identify the mechanisms responsible for these genome-wide DNA methylation alterations, we measured the gene expression levels of several DNA methyltransferases (DNMTs) and their interacting proteins by TaqMan qPCR and observed increased expression of DNMT3A2, DNMT3B, and EZH2 in tumors. Subsequent transient transfection assays in cultured primary prostate cells revealed that DNMT3B1 and DNMT3B2 overexpression resulted in increased methylation of a substantial subset of CpG sites that also showed tumor-specific increased methylation. Bisulfite converted DNA from 193 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2. The tissue samples (first 181) and the cultured cell samples (last 12) were normalized independently.
2011-04-19 | E-GEOD-26126 | biostudies-arrayexpress
Project description:DNA methylation profiling of normal prostates from organ donors and prostate cancer metastases from a rapid autopsy cohort of lethal metastatic prostate cancer Multiple anatomically distinct metastases from each of five patients. Normal prostate samples from organ donors
2013-02-04 | E-GEOD-38073 | biostudies-arrayexpress