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.
Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays
Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays
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.
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.