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| Status |
Public on Jul 01, 2011 |
| Title |
ChIP-seq defined genome-wide map of TGFbeta/SMAD4 targets: implications with clinical outcome of ovarian cancer patients |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by array
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| Summary |
Deregulation of the transforming growth factor-β (TGFβ) signaling pathway in epithelial ovarian cancer has been reported, but the precise mechanism underlying disrupted TGFβ signaling in the disease remains unclear. We performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate genome-wide screening of TGFβ-induced SMAD4 binding in epithelial ovarian cancer. Following TGFβ stimulation of the A2780 epithelial ovarian cancer cell line, we identified 2,362 SMAD4 binding loci and 318 differentially expressed SMAD4 target genes. Comprehensive examination of SMAD4-bound loci, revealed four distinct binding patterns: 1) Basal; 2) Shift; 3) Stimulated Only; 4) Unstimulated Only. SMAD4-bound loci were primarily classified as either Stimulated only (74%) or Shift (25%), indicating that TGFβ-stimulation alters SMAD4 binding patterns in epithelial ovarian cancer cells compared to normal epithelial cells. Furthermore, based on gene regulatory network analysis, we determined that the TGFβ-induced SMAD4-dependent regulatory network was strikingly different in ovarian cancer compared to normal cells. Importantly, the TGFβ/SMAD4 target genes identified in the A2780 epithelial ovarian cancer cell line were predictive of patient survival, based on in silico mining of publically available patient data bases. In conclusion, our data highlight the utility of next generation sequencing technology to identify genome-wide SMAD4 target genes in epithelial ovarian cancer. The results link aberrant TGFβ/SMAD signaling to ovarian tumorigenesis. Furthermore, the identified SMAD4 binding loci, combined with gene expression profiling and in silico data mining of patient cohorts, may provide a powerful approach to determine potential gene signatures with biological and future translational research in ovarian and other cancers.
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| Overall design |
ChIP-Seq: 1 control lane. 4 unstimulated lanes 4 stimulated lanes
Gene expression: 3 technical replicates each of SMAD4 stimulated and SMAD4 unstimulated cells
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| Contributor(s) |
Kennedy BA, Deatherage D, Gu F, Tang B, Chan MW, Nephew KP, Huang TH, Jin VX |
| Citation(s) |
21799915 |
| Submission date |
Feb 25, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Brian Alexander Kennedy |
| E-mail(s) |
kennedy.642@osu.edu
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| Organization name |
The Ohio State University
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| Street address |
278 Chittenden AVE
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| City |
Columbus |
| State/province |
Ohio |
| ZIP/Postal code |
43201 |
| Country |
USA |
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| Platforms (2) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA137115 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27526_RAW.tar |
3.0 Gb |
(http)(custom) |
TAR (of BED, CEL, TXT) |
| Raw data provided as supplementary file |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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