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Androgen receptor-binding sites are highly mutated in prostate cancer

Author

Listed:
  • Tunç Morova

    (Koç University
    University of British Columbia)

  • Daniel R. McNeill

    (National Institute on Aging, NIH)

  • Nada Lallous

    (University of British Columbia)

  • Mehmet Gönen

    (Koç University
    Koç University)

  • Kush Dalal

    (University of British Columbia)

  • David M. Wilson

    (National Institute on Aging, NIH
    Hasselt University)

  • Attila Gürsoy

    (Koç University)

  • Özlem Keskin

    (Koç University)

  • Nathan A. Lack

    (Koç University
    University of British Columbia
    Koç University)

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.

Suggested Citation

  • Tunç Morova & Daniel R. McNeill & Nada Lallous & Mehmet Gönen & Kush Dalal & David M. Wilson & Attila Gürsoy & Özlem Keskin & Nathan A. Lack, 2020. "Androgen receptor-binding sites are highly mutated in prostate cancer," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14644-y
    DOI: 10.1038/s41467-020-14644-y
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    Cited by:

    1. Shuji Ito & Xiaoxi Liu & Yuki Ishikawa & David D. Conti & Nao Otomo & Zsofia Kote-Jarai & Hiroyuki Suetsugu & Rosalind A. Eeles & Yoshinao Koike & Keiko Hikino & Soichiro Yoshino & Kohei Tomizuka & Mo, 2023. "Androgen receptor binding sites enabling genetic prediction of mortality due to prostate cancer in cancer-free subjects," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Jeroen Kneppers & Tesa M. Severson & Joseph C. Siefert & Pieter Schol & Stacey E. P. Joosten & Ivan Pak Lok Yu & Chia-Chi Flora Huang & Tunç Morova & Umut Berkay Altıntaş & Claudia Giambartolomei & Ji, 2022. "Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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