Genomic correlates of clinical outcome in advanced prostate cancer.

Abida, Wassim; Cyrta, Joanna; Heller, Glenn; Prandi, Davide; Armenia, Joshua; Coleman, Ilsa; Cieslik, Marcin; Benelli, Matteo; Robinson, Dan; Van Allen, Eliezer M; Sboner, Andrea; Fedrizzi, Tarcisio; Mosquera, Juan Miguel; Robinson, Brian D; De Sarkar, Navonil; Kunju, Lakshmi P; Tomlins, Scott; Wu, Yi Mi; Nava Rodrigues, Daniel; Loda, Massimo; ... (2019). Genomic correlates of clinical outcome in advanced prostate cancer. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 116(23), pp. 11428-11436. National Academy of Sciences NAS 10.1073/pnas.1902651116

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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 (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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Cyrta, Joanna and Rubin, Mark Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

19 Dec 2019 15:08

Last Modified:

19 Dec 2019 15:08

Publisher DOI:

10.1073/pnas.1902651116

PubMed ID:

31061129

Uncontrolled Keywords:

biomarkers castration-resistant prostate cancer clinical outcomes integrative genomics

BORIS DOI:

10.7892/boris.136291

URI:

https://boris.unibe.ch/id/eprint/136291

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