title: Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone.
abstract: BACKGROUND
  This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test.
  
  
  RESULTS
  Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively).
  
  
  CONCLUSIONS
  CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Salvi
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Casadio
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Conteduca
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: S L
authors.initials: SL
authors.lastname: Burgio
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Menna
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Rossi
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Carretta
authors.affiliation: Pharmacy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Masini
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Calistri
authors.affiliation: The Institute of Cancer Research and the Royal Marsden, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Attard
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: U
authors.initials: U
authors.lastname: De Giorgi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000627:therapeutic use*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D011944:Receptors, Androgen / Q000097:blood* / Q000235:genetics; D012189:Retrospective Studies; D013254:Steroid 17-alpha-Hydroxylase / Q000097:blood* / Q000235:genetics
chemical_list: C410798:AR protein, human; D000736:Androstenes; D011944:Receptors, Androgen; D004247:DNA; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; C089740:abiraterone