Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Epigenomic alterations in localized and advanced prostate cancer

ABSTRACT: Here we used Illumina NGS for high-throughput profiling of the DNA methylome in seven human benign prostate tissues, seven human primary prostate cancer and six human castration resistant prostate cancer patient samples. These data were used to profile the CpG cytosine methylation pattern at single base resolution in each sample and to determine differentially methylated cytosines and regions among samples. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS, MspI,150M-bM-^@M-^S400 bp size fractions) of 20 human prostate tissues (benign prostate tissues, localized and metastatic prostate cancer)

ORGANISM(S): Homo sapiens

SUBMITTER: Pei-Chun Lin

PROVIDER: E-GEOD-41701 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Epigenomic alterations in localized and advanced prostate cancer.

Lin Pei-Chun PC Giannopoulou Eugenia G EG Park Kyung K Mosquera Juan Miguel JM Sboner Andrea A Tewari Ashutosh K AK Garraway Levi A LA Beltran Himisha H Rubin Mark A MA Elemento Olivier O

Neoplasia (New York, N.Y.) 20130401 4

Although prostate cancer (PCa) is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, ...[more]

PMID: 23555183

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Project description:We conducted a genome-wide DNA methylation analysis in CD19+ B-cells from CLL patient and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1764 gene promoters were identified as being differentially methylated between the two groups. Aberrant hypermethylation was found in all HOX gene clusters and a significant number of WNT signaling pathway genes. The genes that were frequently hypermethylated were typically associated with histone H3 lysine 27 tri-methylation or bivalent domains in normal B-cells. An additional 152 genes were found to be differentially methylated between normal naïve and memory B-cells. Of these 152 genes, 123 were hypomethylated in memory B-cells when compared to naïve B-cells. Overall, CLL B-cells had methylation patterns more similar to memory B-cells than naïve B-cells. Cluster analysis showed that the tissue-specific methylated genes separated CLL samples into two groups with differential ZAP70 methylation status. Hypomethylation occurred more frequently in the gene body including introns, exons, and 3'-UTRs in CLL. The hypomethylation in the NFATc1 P2 promoter and first intron correlated with up-regulation of both NFATc1 RNA and protein expression levels in CLL suggesting that an epigenetic mechanism is involved in the constitutive activation of NFAT activity in CLL cells. This comprehensive DNA methylation map will further our understanding of the epigenetic contribution to cellular dysfunction in CLL. To perform a genome-wide analysis of DNA methylation in CLL, we applied the Reduced Representation Bisulfite Sequencing (RRBS) to CD19+ B-cells isolated from normal control and CLL peripheral blood samples. The genomic DNA from each sample was digested with the methylation-insensitive restriction enzyme MspI (restriction site, CCGG) and ligated to Illumina sequencing adaptors containing methylated cytosine residues. The ligated MspI fragments were size-selected, treated with sodium bisulfite, and amplified by PCR. The PCR products were purified and sequenced using Illumina GAIIx sequencer with a read length of 52 or 76bp. 11 CLL B-cell samples, 3 normal control samples including one each of normal CD19+, CD19+/ IgD+ naïve, and CD19+/CD27+ memory B-cell sample and three CLL cell lines (Mec-1, Mec-2, and Wac-3) were used. We generated 20-30 million Illumina sequencing reads for each sample.

Dataset Information

Epigenomic alterations in localized and advanced prostate cancer

Publications

Epigenomic alterations in localized and advanced prostate cancer.

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