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Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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Abstract

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

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Author notes

  1. These authors contributed equally: Surendra Dasari, Michael R. McCarthy.

Authors and Affiliations

  1. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA

    Surendra Dasari

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Michael R. McCarthy, Antonina A. Wojcik, Beth A. Pitel, Arpan Samaddar, Burak Tekin, Rumeal D. Whaley, Aditya Raghunathan, Loren Herrera Hernandez, Rafael E. Jimenez, Kevin C. Halling, John C. Cheville, Benjamin R. Kipp & Sounak Gupta

  3. Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA

    Brad J. Stish

  4. Department of Urology, Mayo Clinic, Rochester, MN, USA

    R. Houston Thompson, Bradley C. Leibovich, Stephen A. Boorjian & R. Jeffrey Karnes

  5. Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Daniel S. Childs, J. Fernando Quevedo, Eugene D. Kwon, Lance C. Pagliaro & Brian A. Costello

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  1. Surendra Dasari
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Contributions

Provision of study materials/patients/data collection: S.D., M.R.M., A.S., B.R.K., and S.G. Data analysis: S.D., M.R.M., A.S., J.C.C., B.R.K., and S.G. Supervision: S.G. Manuscript writing: S.D., M.R.M., A.A.W., B.A.P., A.S., B.T., R.D.W., A.R., L.H.H., R.E.J., B.J.S., R.H.T., B.C.L., S.A.B., R.J.K., D.S.C., J.F.Q., E.D.K., L.C.P., B.A.C., K.C.H., J.C.C., B.R.K., and S.G. All authors reviewed the paper and agreed to the final version of the manuscript.

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Correspondence to Sounak Gupta.

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Dasari, S., McCarthy, M.R., Wojcik, A.A. et al. Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients. Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-024-00814-2

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  • DOI: https://doi.org/10.1038/s41391-024-00814-2

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