University of Utah School of Medicine, Salt Lake City, UT, USA.
Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
Oncologist. 2022 Oct 1;27(10):e815-e818. doi: 10.1093/oncolo/oyac176.
Advanced prostate cancer (aPC) in Black men was reported to present with aggressive features and to be associated with poor prognosis. Herein, we compared the cell-free DNA (cfDNA) genomic landscape of aPC in Black vs White men. Patients (pts) with aPC from 6 academic institutions and available cfDNA comprehensive genomic profiling (CGP) were included. Association between mutated genes and race was evaluated using Barnard's test and a Probabilistic Graphical Model (PGM) machine learning approach. Analysis included 743 aPC pts (217 Black, 526 White) with available cfDNA CGP. The frequency of alterations in the androgen receptor gene was significantly higher in Black vs White men (55.3% vs 35% respectively, P < .001). Additionally, alterations in EGFR, MYC, FGFR1, and CTNNB1 were present at higher frequencies in Black men. PGM analysis and Barnard's test were concordant. Findings from the largest cohort of Black men with aPC undergoing cfDNA CGP may guide further drug development in these men.
黑人中晚期前列腺癌(aPC)表现出侵袭性特征,并与预后不良相关。本研究比较了黑人与白人男性中晚期前列腺癌患者的游离 DNA(cfDNA)基因组图谱。纳入了来自 6 个学术机构的晚期前列腺癌患者和可用的 cfDNA 全面基因组分析(CGP)。使用 Barnard 检验和概率图模型(PGM)机器学习方法评估突变基因与种族之间的关联。分析包括 743 名具有可用 cfDNA CGP 的晚期前列腺癌患者(217 名黑人,526 名白人)。黑人患者中雄激素受体基因突变的频率明显高于白人患者(分别为 55.3%和 35%,P<0.001)。此外,黑人患者中 EGFR、MYC、FGFR1 和 CTNNB1 的改变频率更高。PGM 分析和 Barnard 检验结果一致。这项针对接受 cfDNA CGP 的最大黑人晚期前列腺癌患者队列的研究结果可能为这些患者的进一步药物研发提供指导。