English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
Add to Basket
 Local TagsRelease HistoryDetailsSummary
  Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

Bu, H., Narisu, N., Schlick, B., Rainer, J., Manke, T., Schäfer, G., et al. (2015). Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites. Human Mutations, 37, 52-64. doi:10.1002/humu.22909.

Item is

 

show all hide all

Basic

show hide
Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-408E-6 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-A8D6-9
Genre: Journal Article

Files

show Files

Locators

show
hide
Locator:
https://onlinelibrary.wiley.com/doi/10.1002/humu.22909 (Publisher version)
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Bu, Huajie1, 2, Author
Narisu, Narisu3, Author
Schlick, Bettina1, 4, Author
Rainer, Johannes5, 6, Author
Manke, Thomas7, 8, Author
Schäfer, Georg1, 9, Author
Pasqualini, Lorenza1, Author
Chines, Peter3, Author
Schweiger, Michal R.7, 10, Author
Fuchsberger, Christian6, 11, Author
Klocker, Helmut, Author
Affiliations:
1Department of Urology, Division of Experimental Urology, Medical University of Innsburck, Innsbruck, Austria, ou_persistent22              
2Research Institute for Biomedical Aging Research, Universit of Innsbruck, Innsbruck, Austria, ou_persistent22              
3Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland, ou_persistent22              
4Oncotyrol, Center for Personalized Cancer Medicine, Innsbruck, Austria, ou_persistent22              
5Biocenter Innsbruck, Section for Molecular Pathophysiology, Medical University of Innsbruck, Innsbruck, Austria, ou_persistent22              
6Center for Biomedicine, EURAC Research, Bolzano, Italy, ou_persistent22              
7Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
8Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestraße 63-73, 14195 Berlin, DE, ou_1433545              
9Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria, ou_persistent22              
10Cologne Center for Genomics, University of Cologne, Cologne, Germany, ou_persistent22              
11Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, ou_persistent22              

Content

show
hide
Free keywords: prostate cancer; risk SNPs; androgen receptor; melanophilin; MLPH; androgen regulation; AR
 Abstract: Genome-wide association studies have identified genomic loci, whose single-nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T>G in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR-binding motif, which is enriched in the neighborhood of canonical androgen-responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor-suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH.

Details

show
hide
Language(s): eng - English
 Dates: 2015-09-28
 Publication Status: Issued
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/humu.22909
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Human Mutations
  Other : Hum Mut
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, N.Y. : Wiley-Liss
Pages: 7 Volume / Issue: 37 Sequence Number: - Start / End Page: 52 - 64 Identifier: ISSN: 1059-7794
CoNE: https://pure.mpg.de/cone/journals/resource/954925597586