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Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone

2015; Springer Nature; Volume: 112; Issue: 10 Linguagem: Inglês

10.1038/bjc.2015.128

1532-1827

Samanta Salvi, Valentina Casadio, Vincenza Conteduca, Salvatore Luca Burgio, Cecilia Menna, E. Bianchi, Lorena Rossi, Elisa Carretta, Carla Masini, D. Amadori, Daniele Calistri, Gerhardt Attard, Ugo De Giorgi,

Radiopharmaceutical Chemistry and Applications

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). 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. 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). CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.