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DNA methylation profiling across six histological states of prostate cancer

ABSTRACT: DNA methylation profiling across six histological states of prostate cancer

PROVIDER: PRJNA660747 | ENA |

REPOSITORIES: ENA

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DNA methylation profiling across six histological states of prostate cancer

Project description:DNA methylation profiling across six histological states of prostate cancer

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DNA methylation profiling across six histological states of prostate cancer

Project description:In spite of its prevalence as one of the world’s leading malignancies, prostate cancer (PCa) continues to evade molecular taxonomic sub-classification. However, gross clinical differences are observed within the umbrella term ‘prostate adenocarcinoma’; the majority of tumors appear indolent in nature, whilst a subset manifest aggressively. Contributing factors towards this resistance to molecular classification are an atypically low mutation frequency and a poorly delineated pathobiology. Conversely, epigenetic changes are evidenced to be amongst the earliest and most-widespread aberrations in PCa . We thus hypothesized that delineating epigenomic alterations during the stepwise progression of PCa would improve our understanding of the disease pathobiology and the molecular underpinning of indolent and aggressive tumors. Herein, we report the first epigenomic roadmap of prostate tumorigenesis, in which we dissected DNA methylation and microRNA expression in enriched epithelial cells across the entire trajectory of PCa, through tumor initiation, primary disease and metastatic dissemination. Infinium Human Methylation450K Beachip (Illumina) technology was employed to assess the methylation status of >485,000 CpG sites throughout the genome across six histological stages of prostate cancer (PCa) tumorigenesis: benign (n=10), proliferative inflammatory atrophy (PIA; n=7), high grade prostatic intra-epithelial neoplasia (HGPIN; n=6), indolent PCa (PCI, n=7), agressive PCa (PCA; n=8) and lethal metastatic PCa (PCM; n=6). Three peripheral blood lymphocytes (PBL) samples were also included for control purposes.

2021-09-01 | GSE157272 | GEO

DNA methylation profiling across six histological states of prostate cancer

Project description:In spite of its prevalence as one of the world’s leading malignancies, prostate cancer (PCa) continues to evade molecular taxonomic sub-classification. However, gross clinical differences are observed within the umbrella term ‘prostate adenocarcinoma’; the majority of tumors appear indolent in nature, whilst a subset manifest aggressively. Contributing factors towards this resistance to molecular classification are an atypically low mutation frequency and a poorly delineated pathobiology. Conversely, epigenetic changes are evidenced to be amongst the earliest and most-widespread aberrations in PCa . We thus hypothesized that delineating epigenomic alterations during the stepwise progression of PCa would improve our understanding of the disease pathobiology and the molecular underpinning of indolent and aggressive tumors. Herein, we report the first epigenomic roadmap of prostate tumorigenesis, in which we dissected DNA methylation and microRNA expression in enriched epithelial cells across the entire trajectory of PCa, through tumor initiation, primary disease and metastatic dissemination. We provide evidence in support of proliferative inflammatory atrophy (PIA) as a precursor lesion, distinct from high-grade prostatic intraepithelial neoplasia (HGPIN) and show that indolent and aggressive tumors display unique sets of epigenetically dysregulated loci, which we further investigated as potential discriminatory markers. This study also establishes the importance of DNA methylation beyond the gene promoter in human cancer, with pronounced intra- and inter-genic CpG methylation observed.

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Histological heterogeneity in primary prostate

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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

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