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Status |
Public on Nov 15, 2010 |
Title |
Agilent expression analysis of LNCaP cells following 5'aza-treatment |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
In this data, genes methylated in LNCaP and significantly overexpressed after 5'Azacytidine treatment of LNCaP cells are assessed by Agilent gene expression microarray as a validation for gene repression mechanism due to methylation change.
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Overall design |
[Gene expression] Two-condition experiment, control DMSO-treated vs. 5'aza-treated LNCaP at two time points (@24 and 48 hours) in replicates.
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Contributor(s) |
Shankar S, Dhanasekaran SM, Kim JH, Chinnaiyan AM |
Citation(s) |
21724842 |
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Submission date |
Nov 15, 2010 |
Last update date |
Feb 22, 2018 |
Contact name |
Jung Kim |
E-mail(s) |
junghk@med.umich.edu
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Organization name |
University of Michigan
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Street address |
1400 E. Medical Center Drive
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City |
Ann Arbor |
State/province |
MI |
ZIP/Postal code |
48109 |
Country |
USA |
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Platforms (1) |
GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE27619 |
Deep sequencing reveals distinct patterns of DNA methylation and transcript isoform regulation in prostate cancer |
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Relations |
BioProject |
PRJNA142533 |