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Series GSE65478 Query DataSets for GSE65478
Status Public on Sep 30, 2015
Title Androgen Receptor profiling in tumor specimens yields hallmarks of prostate cancer outcome
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Prostate cancer is the most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, since high-risk patients may benefit from additional therapy at early stages of the disease, greatly increasing the chance for cure. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression.  In addition, we identified a distinct Androgen Receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential Androgen Receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential in another cohort of prostate cancer patients. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through integration of multilevel genomic data on chromatin accessibility and transcriptional regulation with publicly available transcriptomic and clinical datastreams. With this, we present a highly innovative pipeline for biomarker discovery that is easily implementable in other fields of oncology. 
Overall design Accessible chromatin was mapped genome-wide by FAIRE-Seq (Formaldehyde-Assisted Isolation of Regulatory Elements) in 4 primary, 3 hormonal therapy-resistant and 3 metastatic prostate cancers, as well as in 4 normal prostate specimens. Androgen receptor (AR) binding to DNA was profiled by ChIP-seq (Chromatin Immunoprecipitation) genome-wide in 4 primary and 3 therapy-resistant prostate tumors.
Contributor(s) Stelloo S, Nevedomskaya E, Bergman AM, Zwart W
Citation(s) 26412853, 26981385
Submission date Jan 30, 2015
Last update date May 15, 2019
Contact name Wilbert Zwart
Organization name Netherlands Cancer Institute
Department Molecular Pathology
Street address Plesmanlaan 121
City Amsterdam
ZIP/Postal code 1066 CX
Country Netherlands
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (26)
GSM1598204 wz369_FAIRE_normal
GSM1598205 wz371_FAIRE_normal
GSM1598206 wz382_FAIRE_normal
BioProject PRJNA274138
SRA SRP053007

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Supplementary file Size Download File type/resource
GSE65478_RAW.tar 2.8 Gb (http)(custom) TAR (of BED, BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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