Genomic correlates of clinical outcome in advanced prostate cancer
Open accessAbstract
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.
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Publicly available gene expression data from a matched cohort of mCRPC was downloaded from cBioportal.
“Publicly available gene expression data from a matched cohort established previously59 or mCRPC was downloaded from cBioportal (20 May 2021)94–96.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [94]
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“Publicly available gene expression data from a matched cohort established previously 59 or mCRPC was downloaded from cBioportal (20 May 2021) 94–96 .”
Self-citation
- Authors
- Abida, W., Cyrta, J., Heller, G., Prandi, D., Armenia, J., Coleman, I., Cieslik, M., Benelli, M., Robinson, D., Van Allen, E. M., Sboner, A., Fedrizzi, T., Mosquera, J. M., Robinson, B. D., De Sarkar, N., Kunju, L. P., Tomlins, S., Wu, Y. M., Nava Rodrigues, D., Loda, M., Gopalan, A., Reuter, V. E., Pritchard, C. C., Mateo, J., Bianchini, D., Miranda, S., Carreira, S., Rescigno, P., Filipenko, J., Vinson, J., Montgomery, R. B., Beltran, H., Heath, E. I., Scher, H. I., Kantoff, P. W., Taplin, M.-E., Schultz, N., deBono, J. S., Demichelis, F., Nelson, P. S., Rubin, M. A., Chinnaiyan, A. M., & Sawyers, C. L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Bern (CH)
- University of Trento (IT)
- University of Washington (US)
- University of Michigan (US)
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215;
- Cornell University (US)
- Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109;
- Institute of Cancer Research, London SW7 3RP, United Kingdom;
- National Health Service (GB)
- Prostate Cancer Clinical Trials Consortium (US)
- Prostate Cancer Clinical Trials Consortium, New York, NY 10065;
- Wayne State University (US)
- Dana-Farber Cancer Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Nelson, Peter S.
- Rubin, Mark A.
- Chinnaiyan, Arul M.
- Sawyers, Charles L.
- ORCID
- Abida, Wassim
- Cyrta, Joanna
- Heller, Glenn
- Prandi, Davide
- Armenia, Joshua
- Coleman, Ilsa
- Cieslik, Marcin
- Benelli, Matteo
- Robinson, Dan
- Sboner, Andrea
- Fedrizzi, Tarcisio
- Mosquera, Juan Miguel
- Robinson, Brian D.
- Kunju, Lakshmi P.
- Tomlins, Scott
- Wu, Yi Mi
- Loda, Massimo
- Gopalan, Anuradha
- Pritchard, Colin C.
- Bianchini, Diletta
- Miranda, Susana
- Carreira, Suzanne
- Rescigno, Pasquale
- Beltran, Himisha
- Heath, Elisabeth I.
- Scher, Howard I.
- Kantoff, Philip W.
- Taplin, Mary-Ellen
- Schultz, Nikolaus
- Demichelis, Francesca
- Nelson, Peter S.
- Rubin, Mark A.
- Chinnaiyan, Arul M.
- Sawyers, Charles L.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-05-06
- Volume
- 116
- Issue
- 23
- Pages
- 11428-11436
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6561293
- OpenAlex
- W2944403040
- Cited by
- 1,372
- References
- 45
- Citations by year
- 2026: 144 · 2025: 199 · 2024: 207 · 2023: 238 · 2022: 185 · 2021: 219 · 2020: 140 · 2019: 39 · 2018: 1
- FWCI
- 107.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by-nc-nd)
- BORIS (University Library Bern) (submittedVersion, cc-by-nc-nd)
- Florence Research (University of Florence) (submittedVersion)
- Open Access CRIS of the University of Bern
- Funders
- Prostate Cancer Foundation (SU2C-AACR-DT0712)
- EIF | Stand Up To Cancer (SU2C-AACR-DT0712)
- Howard Hughes Medical Institute (none)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- metastatic castration-resistant prostate cancer, RB1 alterations, androgen receptor pathway inhibitors, abiraterone, enzalutamide, TP53, neuroendocrine prostate cancer, prognostic factors, time on treatment, survival, tumor genomic heterogeneity, gene expression profiling
- MeSH terms
- Aged, Androstenes, Benzamides, Humans, Male, Middle Aged, Nitriles, Phenylthiohydantoin, Receptors, Androgen, Biomarkers, Tumor, Treatment Outcome, Drug Resistance, Neoplasm, Genomics, Prostatic Neoplasms, Castration-Resistant
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