Soh Pamela X Y, Adams Alice, Bornman M S Riana, Jiang Jue, Stricker Phillip D, Mutambirwa Shingai B A, Jaratlerdsiri Weerachai, Hayes Vanessa M
Ancestry and Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia.
Faculty of Science, University of Bath, BA2 7AY Bath, UK.
iScience. 2025 Apr 15;28(5):112437. doi: 10.1016/j.isci.2025.112437. eCollection 2025 May 16.
Prostate cancer (PCa) is marked by significant ancestral bias, with African men disproportionately impacted. However, genome profiling studies have yet to explore the mutational landscape and disparity contribution of the male-determining Y chromosome. Using a cohort of 106 African and 57 European PCa cases, biased toward aggressive presenting primary disease, we performed complete Y chromosome interrogation for inherited and somatic variance. Capturing unexplored early-diverged Y-haplogroup substructure, while European men are 3.1-fold more likely to present with a rare potentially deleterious germline variant, a higher proportion of African patients acquired Y chromosome tumorigenic events (26.4% African, 14% European). While somatic copy number alterations were universally more common to aggressive tumors, besides shared alterations impacting and , African derived tumors were prone to somatic losses associated with , , and . This much-needed African inclusive study alludes to possible Y chromosome contribution, at least in part, to treatment resistance and worsened mortality rates in African men.
前列腺癌（PCa）具有显著的祖先偏向性，非洲男性受影响的比例过高。然而，基因组图谱研究尚未探索男性决定因素Y染色体的突变格局和差异贡献。我们使用了一组106例非洲和57例欧洲PCa病例，这些病例倾向于侵袭性原发性疾病，对Y染色体进行了全面的遗传和体细胞变异检测。在捕捉未被探索的早期分化Y单倍群亚结构时，虽然欧洲男性携带罕见潜在有害种系变异的可能性高3.1倍，但更高比例的非洲患者发生了Y染色体致瘤事件（非洲患者为26.4%，欧洲患者为14%）。虽然体细胞拷贝数改变在侵袭性肿瘤中普遍更为常见，但除了影响 和 的共同改变外，非洲来源的肿瘤更容易发生与 、 和 相关的体细胞缺失。这项急需纳入非洲人群的研究表明，Y染色体可能至少部分导致了非洲男性的治疗抵抗和死亡率上升。
