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Genomic correlates of clinical outcome in advanced prostate cancer

2019; National Academy of Sciences; Volume: 116; Issue: 23 Linguagem: Inglês

10.1073/pnas.1902651116

1091-6490

Wassim Abida, Joanna Cyrta, Glenn Heller, Davide Prandi, Joshua Armenia, Ilsa M. Coleman, Marcin Cieślik, Matteo Benelli, Dan R. Robinson, Eliezer M. Van Allen, Andrea Sboner, Tarcisio Fedrizzi, Juan Miguel Mosquera, Brian D. Robinson, Navonil De Sarkar, Lakshmi P. Kunju, Scott A. Tomlins, Yi Mi Wu, Daniel Nava Rodrigues, Massimo Loda, Anuradha Gopalan, Victor E. Reuter, Colin C. Pritchard, Joaquı́n Mateo, Diletta Bianchini, Susana Miranda, Suzanne Carreira, Pasquale Rescigno, Julie Filipenko, Jacob Vinson, Bruce Montgomery, Himisha Beltran, Elisabeth I. Heath, Howard I. Scher, Philip W. Kantoff, Mary‐Ellen Taplin, Nikolaus Schultz, Johann S. de Bono, Francesca Demichelis, Peter S. Nelson, Mark A. Rubin, Arul M. Chinnaiyan, Charles L. Sawyers,

Cancer, Lipids, and Metabolism

Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about the impact of this heterogeneity on clinical outcome. Here, we report comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer (mCRPC) linked with longitudinal clinical outcomes, integrating findings from whole-exome, transcriptome, and histologic analysis. For 128 patients treated with a first-line next-generation androgen receptor signaling inhibitor (ARSI; abiraterone or enzalutamide), we examined the association of 18 recurrent DNA- and RNA-based genomic alterations, including androgen receptor (