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Androgen receptor profiling predicts prostate cancer outcome.

Stelloo S, Nevedomskaya E, van der Poel HG, de Jong J, van Leenders GJ, Jenster G, Wessels LF, Bergman AM, Zwart W - EMBO Mol Med (2015)

Bottom Line: Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively.These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential.By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

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Related in: MedlinePlus

Genomics-based pipeline for biomarker discovery and validationTissue samples were processed for FAIRE-seq, and transcription factor (TF) motifs in open chromatin regions were analyzed. Selected transcription factor was mapped with ChIP-seq (in this case androgen receptor) to identify sites that are differentially bound between two sample groups. The target genes of the differential binding regions were coupled to gene expression and survival data and further refined into a minimal gene signature, which was validated in a number of gene expression datasets.
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fig01: Genomics-based pipeline for biomarker discovery and validationTissue samples were processed for FAIRE-seq, and transcription factor (TF) motifs in open chromatin regions were analyzed. Selected transcription factor was mapped with ChIP-seq (in this case androgen receptor) to identify sites that are differentially bound between two sample groups. The target genes of the differential binding regions were coupled to gene expression and survival data and further refined into a minimal gene signature, which was validated in a number of gene expression datasets.

Mentions: By combining existing technologies, we here propose a genomics pipeline for biomarker discovery (Fig1) and showed its application in prostate cancer, aimed at identification of prostate cancer patients with a high-risk of metastatic relapse. Firstly, transcription factor involvement was identified through motif analysis on open chromatin regions. Accessible regions were analyzed to reveal enrichment of a binding motif for a certain transcription factor involved in disease (prostate cancer). Actual transcription factor binding was mapped with ChIP-seq to identify sites that are differentially bound between two sample groups. As a proof-of-principle, we assessed AR chromatin binding profiles in this study. The target genes of the differential binding regions were subsequently coupled to gene expression data in cell lines to uncover genuine involvement of the transcription factor in expression of a distinct gene set. This gene set was subsequently tested for association with survival data of patients, and further refined into a minimal gene signature.


Androgen receptor profiling predicts prostate cancer outcome.

Stelloo S, Nevedomskaya E, van der Poel HG, de Jong J, van Leenders GJ, Jenster G, Wessels LF, Bergman AM, Zwart W - EMBO Mol Med (2015)

Genomics-based pipeline for biomarker discovery and validationTissue samples were processed for FAIRE-seq, and transcription factor (TF) motifs in open chromatin regions were analyzed. Selected transcription factor was mapped with ChIP-seq (in this case androgen receptor) to identify sites that are differentially bound between two sample groups. The target genes of the differential binding regions were coupled to gene expression and survival data and further refined into a minimal gene signature, which was validated in a number of gene expression datasets.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644377&req=5

fig01: Genomics-based pipeline for biomarker discovery and validationTissue samples were processed for FAIRE-seq, and transcription factor (TF) motifs in open chromatin regions were analyzed. Selected transcription factor was mapped with ChIP-seq (in this case androgen receptor) to identify sites that are differentially bound between two sample groups. The target genes of the differential binding regions were coupled to gene expression and survival data and further refined into a minimal gene signature, which was validated in a number of gene expression datasets.
Mentions: By combining existing technologies, we here propose a genomics pipeline for biomarker discovery (Fig1) and showed its application in prostate cancer, aimed at identification of prostate cancer patients with a high-risk of metastatic relapse. Firstly, transcription factor involvement was identified through motif analysis on open chromatin regions. Accessible regions were analyzed to reveal enrichment of a binding motif for a certain transcription factor involved in disease (prostate cancer). Actual transcription factor binding was mapped with ChIP-seq to identify sites that are differentially bound between two sample groups. As a proof-of-principle, we assessed AR chromatin binding profiles in this study. The target genes of the differential binding regions were subsequently coupled to gene expression data in cell lines to uncover genuine involvement of the transcription factor in expression of a distinct gene set. This gene set was subsequently tested for association with survival data of patients, and further refined into a minimal gene signature.

Bottom Line: Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively.These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential.By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Show MeSH
Related in: MedlinePlus