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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DNA methylation sensitivity at detecting cancer in prostate core biopsies [DNA Methylation Profiles]

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Krzysztof Goryca

PROVIDER: E-GEOD-55598 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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DNA methylation sensitivity at detecting cancer in prostate core biopsies [DNA Methylation Profiles]

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.

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DNA methylation profiling reveals novel biomarkers and important roles for DNA methyltransferases in prostate cancer

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.

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2019-03-04 | GSE78904 | GEO

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