尽管中国和西方患者在前列腺癌发病率和死亡率上存在着明显差异，但对其潜在基因组差异的研究还相对缺乏。本临床-基因组学研究旨在揭示不同种族间前列腺癌差异所致基因组突变，并探究中国前列腺癌患者的突变谱。我们招募了1016名中国前列腺癌患者进行前瞻性研究，并对他们进行靶向测序，最终得到了859名患者41个基因的可用测序数据。作为西方男性的比较组，我们从癌症基因组图谱项目（The Cancer Genome Atlas，TCGA，局部区域性前列腺癌）、斯隆-凯特琳癌症中心（Memorial Sloan Kettering Cancer Center，MSKCC，转移性门源性前列腺癌）和挺身面对癌症组织（Stand Up To Cancer，SU2C，转移性门静脉抗性前列腺癌）的基因组数据作为参照。我们采用一种综合生物信息学策略分析了基因组突变。疾病阶段的对比结果显示在转移性门静脉抗性前列腺癌中，肿瘤蛋白53（TP53）、雄激素受体（AR）、Forkhead Box A1（FOXA1）和与细胞周期通路相关的基因突变富集。腺瘤性息肉样大肠癌（APC）基因突变在有内脏转移的患者中更常见。西方男性与中国男性之间的基因组差异主要存在于门源性前列腺癌，而中国男性的局部区域性前列腺癌中FOXA1（11.4% vs 4.2%）突变更多但TP53（4.8% vs 13%）突变较少，在转移性门源性前列腺癌阶段中TP53（11% vs 29.2%）、磷酸酶和张力调节蛋白（PTEN；2.5% vs 10.3%）和APC（1.7% vs 7.4%）突变都较少。两种种族的转移性门静脉抗性前列腺癌患者的突变谱相似。此外，相较于西方队列，FOXA1第2类突变在中国队列中较少，且在转移过程中未发现富集。我们的研究为更好地了解中国的前列腺癌提供了宝贵资源，并揭示了相关的基因组变异与种族间前列腺癌差异的关联。本文受版权保护。保留所有权利。

Although there is a well-known disparity in prostate cancer (PC) incidence and mortality between Chinese and Western patients, the underlying genomic differences have been investigated only sparsely. This clinico-genomic study was conducted to reveal the genomic mutations contributing to the PC disparity across ethnicities and investigate the mutational profile of Chinese PC patients. A total of 1016 Chinese PC patients were prospectively enrolled and subjected to targeted sequencing, resulting in usable sequencing data for 41 genes from 859 patients. Genomic data retrieved from The Cancer Genome Atlas (TCGA; locoregional PC), Memorial Sloan Kettering Cancer Center [MSKCC; metastatic castration-sensitive PC (mCSPC)] and Stand Up To Cancer [SU2C; metastatic castration-resistant PC (mCRPC)] cohorts were used as comparators representing Western men. Genomic mutations were analyzed using an integrated bioinformatic strategy. A comparison of the disease stages revealed that mutations in tumor protein 53 (TP53), androgen receptor (AR), forkhead box A1 (FOXA1) and genes involved in the cell cycle pathway were enriched in mCRPC. Mutations in adenomatous polyposis coli (APC) gene were found to be more prevalent in patients with visceral metastasis. Genomic differences between Western and Chinese men were mainly observed in castration-sensitive PC, with tumors from Chinese men having more FOXA1 (11.4% vs 4.2%) but fewer TP53 (4.8% vs 13%) mutations in locoregional PC and harboring fewer TP53 (11% vs 29.2%), phosphatase and tensin homolog (PTEN; 2.5% vs 10.3%) and APC (1.7% vs 7.4%) mutations in the mCSPC stage than those of Western men. Patients of both ethnicities with mCRPC had similar mutational spectra. Furthermore, FOXA1 class-2 was less common than FOXA1 class-1 and showed no enrichment in metastasis, contrary to the findings in the Western cohort. Our study provides a valuable resource for a better understanding of PC in China and reveals the genomic alterations associated with PC disparity across races.This article is protected by copyright. All rights reserved.