Androgen receptor-binding sites are highly mutated in prostate cancer

Tunç Morova, Daniel R. McNeill, Nada Lallous, Mehmet Gönen, Kush Dalal, David M. Wilson, Attila Gürsoy, Özlem Keskin, Nathan A. Lack

Research output: Contribution to journalArticle

Abstract

Androgen receptor (AR) signalling is essential in nearly all prostate cancers. Any alterations to AR-mediated transcription can have a profound effect on carcinogenesis and tumor growth. While mutations of the AR protein have been extensively studied, little is known about those somatic mutations that occur at the non-coding regions where AR binds DNA. Using clinical whole genome sequencing, we show 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 were also found to have elevated rate of mutations in breast cancer. We provide evidence that these mutations at AR binding sites, and likely other related transcription factors, are caused by faulty repair of abasic sites. Overall, this work demonstrates that non-coding AR binding sites are frequently mutated in prostate cancer and can impact enhancer activity.

Original languageEnglish (US)
Article number832
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Morova, T., McNeill, D. R., Lallous, N., Gönen, M., Dalal, K., Wilson, D. M., Gürsoy, A., Keskin, Ö., & Lack, N. A. (2020). Androgen receptor-binding sites are highly mutated in prostate cancer. Nature communications, 11(1), [832]. https://doi.org/10.1038/s41467-020-14644-y