title: Androgen receptor alterations in prostate cancer relapsed during a combined androgen blockade by orchiectomy and bicalutamide.
abstract: Mechanisms of prostate cancer (CaP) recurrence during a combined androgen blockade (CAB) are poorly understood. Previously, the role of androgen receptor (AR) gene mutations underlying the CAB therapy relapse has been raised. To investigate the hypothesis that AR gene aberrations are involved in CAB relapse, 11 locally recurrent CaP samples from patients treated with orchiectomy and bicalutamide were analyzed for copy number changes and DNA sequence alterations of the AR gene by fluorescence in situ hybridization and single-strand conformation polymorphism, respectively. Altogether, base changes were detected in four tumors (36%). Three of them were missense mutations (G166S, W741C, M749I) and two were silent polymorphisms. Interestingly, none of the tumors had AR amplification. These data suggest that different AR variants are developed and selected for during various types of hormonal treatments, and also, that CAB achieved by orchiectomy and bicalutamide does not act as a selective force for AR amplification.
authors.affiliation: Department of Clinical Genetics, Tampere University Hospital, Tampere, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Haapala
authors.forename: E R
authors.initials: ER
authors.lastname: Hyytinen
authors.forename: M
authors.initials: M
authors.lastname: Roiha
authors.forename: M
authors.initials: M
authors.lastname: Laurila
authors.forename: I
authors.initials: I
authors.lastname: Rantala
authors.forename: H J
authors.initials: HJ
authors.lastname: Helin
authors.forename: P A
authors.initials: PA
authors.lastname: Koivisto
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009570:Nitriles; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D011944:Receptors, Androgen / Q000235:genetics*; D014105:Tosyl Compounds
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide