title: Prostate cancer genetic-susceptibility locus on chromosome 20q13 is amplified and coupled to androgen receptor-regulation in metastatic tumors.
abstract: The 20q13 chromosomal region has been previously identified as the hereditary prostate cancer genetic-susceptibility locus on chromosome 20 (HPC20). In this study, the 20q13 region was shown to be frequently co-amplified with the androgen receptor (AR) in metastatic prostate cancer. Furthermore, the AR signaling 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 of most genes located on the 20q13 CAR. Moreover, amplification of AR 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-resistant metastatic disease.
  
  
  CONCLUSIONS
  These novel results are a noteworthy example of the cross-talk between gene amplification and gene transcription in the development of advanced prostate cancer.
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue, Room 617, Montréal, QC, Canada H3A 1A3. michel.tremblay@mcgill.ca.
authors.forename: David P
authors.initials: DP
authors.lastname: Labbé
authors.forename: Dawid G
authors.initials: DG
authors.lastname: Nowak
authors.forename: Geneviève
authors.initials: G
authors.lastname: Deblois
authors.forename: Laurent
authors.initials: L
authors.lastname: Lessard
authors.forename: Vincent
authors.initials: V
authors.lastname: Giguère
authors.forename: Lloyd C
authors.initials: LC
authors.lastname: Trotman
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
mesh_terms: D045744:Cell Line, Tumor; D002890:Chromosomes, Human, Pair 20; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen