Abida, WassimWassimAbidaCyrta, JoannaJoannaCyrtaHeller, GlennGlennHellerPrandi, DavideDavidePrandiArmenia, JoshuaJoshuaArmeniaColeman, IlsaIlsaColemanCieslik, MarcinMarcinCieslikBenelli, MatteoMatteoBenelliRobinson, DanDanRobinsonVan Allen, Eliezer MEliezer MVan AllenSboner, AndreaAndreaSbonerFedrizzi, TarcisioTarcisioFedrizziMosquera, Juan MiguelJuan MiguelMosqueraRobinson, Brian DBrian DRobinsonDe Sarkar, NavonilNavonilDe SarkarKunju, Lakshmi PLakshmi PKunjuTomlins, ScottScottTomlinsWu, Yi MiYi MiWuNava Rodrigues, DanielDanielNava RodriguesLoda, MassimoMassimoLodaGopalan, AnuradhaAnuradhaGopalanReuter, Victor EVictor EReuterPritchard, Colin CColin CPritchardMateo, JoaquinJoaquinMateoBianchini, DilettaDilettaBianchiniMiranda, SusanaSusanaMirandaCarreira, SuzanneSuzanneCarreiraRescigno, PasqualePasqualeRescignoFilipenko, JulieJulieFilipenkoVinson, JacobJacobVinsonMontgomery, Robert BRobert BMontgomeryBeltran, HimishaHimishaBeltranHeath, Elisabeth IElisabeth IHeathScher, Howard IHoward IScherKantoff, Philip WPhilip WKantoffTaplin, Mary-EllenMary-EllenTaplinSchultz, NikolausNikolausSchultzdeBono, Johann SJohann SdeBonoDemichelis, FrancescaFrancescaDemichelisNelson, Peter SPeter SNelsonRubin, Mark AndrewMark AndrewRubinChinnaiyan, Arul MArul MChinnaiyanSawyers, Charles LCharles LSawyers2024-10-282024-10-282019-06-04https://boris-portal.unibe.ch/handle/20.500.12422/184142Heterogeneity 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 (AR) variant expression, AR transcriptional output, and neuroendocrine expression signatures, with clinical outcomes. Of these, only RB1 alteration was significantly associated with poor survival, whereas alterations in RB1, AR, and TP53 were associated with shorter time on treatment with an ARSI. This large analysis integrating mCRPC genomics with histology and clinical outcomes identifies RB1 genomic alteration as a potent predictor of poor outcome, and is a community resource for further interrogation of clinical and molecular associations.enbiomarkers castration-resistant prostate cancer clinical outcomes integrative genomics600 - Technology::610 - Medicine & healtharticle10.7892/boris.1362913106112910.1073/pnas.1902651116