Effect of HOXB13 and FOXA1 on the AR cistrome during prostate tumorigenesis in primary human tissue.

5018 Background: The androgen receptor (AR) is central to prostate carcinogenesis and cancer progression. Current understanding of the prostate AR cistrome - the genome-wide set of AR binding sites (ARBS) - is driven largely by tumor model systems. The role of the AR cistrome in prostate tumorigenesis in human tissue is unknown. We map the AR cistrome in 20 normal and tumor human prostate samples using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Methods: Chromatin was extracted from 13 tumor and 7 matched histologically normal foci (>70% enrichment) from fresh-frozen radical prostatectomy specimens. Tissue was pulverized, fixed and sonicated then immunoprecipitated with antibody to AR; DNA was isolated; libraries were constructed for the Illumina platform; sequencing reads were aligned to the human genome using MACS (false discovery rate 0.01) Results: Median 19,602 ARBS were called per sample. In unsupervised pairwise analysis of each AR cistrome, specimens clustered ...