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Series GSE114385 Query DataSets for GSE114385
Status Public on May 15, 2018
Title A somatically acquired enhancer of the androgen receptor is a noncoding driver in advanced prostate cancer
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a somatically acquired AR enhancer located 650 kilobases centromeric to the AR. Systematic perturbation of this enhancer using genome editing decreased proliferation by suppressing AR levels. Insertion of an additional copy of this region sufficed to increase proliferation under low androgen conditions and to decrease sensitivity to enzalutamide. Epigenetic data generated in localized prostate tumors and benign specimens support the notion that this region is a developmental enhancer. Collectively, these observations underscore the importance of epigenomic profiling in primary specimens and the value of deploying genome editing to functionally characterize noncoding elements. More broadly, this work identifies a therapeutic vulnerability for targeting the AR and emphasizes the importance of regulatory elements as highly recurrent oncogenic drivers.
 
Overall design Examination of H3K4me2 in 4 patient tumors, H3K27me3 in 4 patient tumors, H3K27Ac in 11 patient tumors, HOXB13 in 4 patient tumors, FOXA1 in 4 patient tumors
 
Contributor(s) Qiu X, Takeda DY, Spisak S, Freedman ML
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Submission date May 14, 2018
Last update date Mar 26, 2019
Contact name Matthew Freedman
E-mail(s) freedman@broadinstitute.org
Organization name Dana Faber Cancer Institute
Street address 450 Brookline Avenue
City Boston
State/province Massachusetts
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (33)
GSM3140880 Localized tumor H3K27Ac_Fig1_T1
GSM3140881 Localized tumor H3K27Ac_Fig1_T2
GSM3140882 Localized tumor H3K27Ac_Fig1_T3
Relations
BioProject PRJNA471255
SRA SRP145590

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE114385_RAW.tar 334.3 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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