|Public on May 03, 2011
|Deep sequencing reveals distinct patterns of DNA methylation and transcript isoform regulation in prostate cancer
|Expression profiling by array
Methylation profiling by genome tiling array
Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in selected prostate tissues and cell lines using Methylplex-Next Generation Sequencing (M-NGS). Hidden Markov Model based next generation sequence analysis identified ~68,000 methylated regions per sample. While global CpG Island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively. We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific, including numerous novel DMRs. A novel cancer specific DMR in WFDC2 promoter showed heavy methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion positive and negative cancers. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.
This SuperSeries is composed of the SubSeries listed below.
|Refer to individual Series.
|Mar 01, 2011
|Last update date
|May 15, 2019
|University of Michigan
|1400 E. Medical Center Drive
|Agilent-014791 Human CpG Island ChIP-on-Chip Microarray 244K (G4492A) (Feature Number version)
|Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
|Illumina Genome Analyzer (Homo sapiens)
|This SuperSeries is composed of the following SubSeries:
|Agilent expression analysis of LNCaP cells following 5'aza-treatment
|Agilent expression analysis of prostate cancer tissue samples
|Agilent CpG array analysis of Methylplex-library of prostate cancer cell lines