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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


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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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).

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