PT  - JOURNAL ARTICLE
AU  - Tunç Morova
AU  - Mehmet Gönen
AU  - Attila Gursoy
AU  - Özlem Keskin
AU  - Nathan A. Lack
TI  - Androgen receptor binding sites are highly mutated in prostate cancer
AID  - 10.1101/225433
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 225433
4099  - http://biorxiv.org/content/early/2017/11/27/225433.short
4100  - http://biorxiv.org/content/early/2017/11/27/225433.full
AB  - Androgen receptor (AR) signalling is essential to nearly all prostate cancer cells. Any alterations to AR-mediated transcription can have a profound effect on prostate carcinogenesis and tumour growth. While the AR protein has been extensively studied, little is know about mutations to the non-coding regions where AR binds to DNA. Using clinical whole genome sequencing, we demonstrate that AR binding sites have a dramatically increased rate of mutations that is greater than any other transcription factor and specific to only prostate cancer. Demonstrating this may be common to lineage-specific transcription factors, estrogen receptor binding sites had an elevated rate of mutations in breast cancer. Based on the mutations observed at the binding site of AR and other related transcription factors, we proposed that AR occupancy impairs access of base excision repair enzymes to endogenous DNA damage. Overall, this work demonstrates that non-coding AR binding sites are frequently mutated in prostate cancer and may potentially act as driver mutations.