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.

原发性前列腺癌 (pPC) 在转变为转移性非去势 (mNC-PC) 和去势抵抗 (mCR-PC) 疾病时，会经历继发于治疗相关选择压力的基因组进化。对 pPC（ n  = 97）、局部晚期疾病（涉及膀胱/直肠，n  = 12）、mNC-PC（n  = 21）和 mCR-PC（n = 54）的下一代测序结果进行了评估 。我们确定了高级 pPC 中TP53改变的富集、HGNE 疾病中TP53/RB1改变以及转移性和去势抵抗性疾病中AR改变。在大约五分之一的病例中发现了可操作的改变（MSI-H 表型和 HRR 基因）。这些结果有助于阐明前列腺癌临床范围内基因组改变的情况。