Prostate cancer genetic-susceptibility locus on chromosome 20q13 is amplified and coupled to androgen receptor-regulation in metastatic tumors

Labbé, D. P., Nowak, D. G., Deblois, G., Lessard, L., Giguère, V., Trotman, L. C., Tremblay, M. L. (2014) Prostate cancer genetic-susceptibility locus on chromosome 20q13 is amplified and coupled to androgen receptor-regulation in metastatic tumors. Molecular Cancer Research, 12 (2). pp. 184-189. ISSN 15417786 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/24379448
DOI: 10.1158/1541-7786.MCR-13-0477

Abstract

The 20q13 chromosomal region has been previously identified as the hereditary prostate cancer geneticsusceptibility locus on chromosome 20 (HPC20). In this study, the 20q13 region was shown to be frequently co-amplified with the androgen receptor (AR) inmetastatic prostate cancer. Furthermore, the ARsignaling axis,which plays an essential role in the pathogenesis of prostate cancer, was demonstrated to be central to the regulation of the 20q13 common amplified region (CAR). High-resolution mapping analyses revealed hot spots of AR recruitment to response elements in the vicinity ofmost genes located on the 20q13CAR.Moreover, amplification ofAR significantly co-occurred with CAR amplification on 20q13 and it was confirmed that the majority of AR-bound genes on the 20q13 CAR were indeed regulated by androgens. These data reveal that amplification of the AR is tightly linked to amplification of the AR-regulated CAR region on 20q13. These results suggest that the cross-talk between gene amplification and gene transcription is an important step in the development of castration-resistantmetastatic disease. Implications: These novel results are a noteworthy example of the cross-talk between gene amplification and gene transcription in the development of advanced prostate cancer. Visual Overview: http://mcr.aacrjournals.org/content/early/2014/02/07/1541-7786.MCR-13-0477/F1.large.jpg.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
diseases & disorders > cancer > metastasis
diseases & disorders > cancer > cancer types > prostate cancer
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL Cancer Center Shared Resources > Animal Services
CSHL labs > Trotman lab
CSHL Cancer Center Shared Resources > Bioinformatics Service
Depositing User: Matt Covey
Date: 2014
Date Deposited: 14 Mar 2014 14:35
Last Modified: 02 Nov 2015 17:37
PMCID: PMC3944382
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29672

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