Androgen receptor-binding sites are highly mutated in prostate cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 02 2020
11 02 2020
Historique:
received:
04
12
2017
accepted:
20
01
2020
entrez:
13
2
2020
pubmed:
13
2
2020
medline:
24
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32047165
doi: 10.1038/s41467-020-14644-y
pii: 10.1038/s41467-020-14644-y
pmc: PMC7012874
doi:
Substances chimiques
AR protein, mouse
0
Receptors, Androgen
0
Receptors, Estrogen
0
Transcription Factors
0
Apex1 protein, mouse
EC 4.2.99.18
DNA-(Apurinic or Apyrimidinic Site) Lyase
EC 4.2.99.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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