University of Texas Southwestern Medical School, Dallas, TX, USA.
Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Oncologist. 2024 Mar 4;29(3):219-226. doi: 10.1093/oncolo/oyad341.
Differences in cancer genomes between racial groups may impact tumor biology and health disparities. However, the discovery of race-associated mutations is constrained by the limited representation and sample size of different racial groups in prior genomic studies. We evaluated the influence of race on the frequency of gene mutations using the Genomics, Evidence, Neoplasia, Information, Exchange database, a large genomic dataset aggregated from clinical sequencing. Matched cohort analyses were used to identify histology-specific race-associated mutations including increased TERT promoter mutations in Black and Asian patients with gliomas and bladder cancers, and a decreased frequency of mutations in DNA repair pathway genes and subunits of the SWI/SNF chromatin complex in Asian and Black patients across multiple cancer types. The distribution of actionable mutations in oncogenes was also race-specific, demonstrating how targeted therapies may have a disparate impact on racial groups. Down-sampling analyses indicate that larger sample sizes are likely to discover more race-associated mutations. These results provide a resource to understand differences in cancer genomes between racial groups which may inform the design of clinical studies and patient recruitment strategies in biomarker trials.
不同种族之间的癌症基因组差异可能会影响肿瘤生物学和健康差异。然而，种族相关突变的发现受到先前基因组研究中不同种族群体代表性和样本量有限的限制。我们使用从临床测序中汇集的大型基因组数据集——Genomics, Evidence, Neoplasia, Information, Exchange 数据库，评估了种族对基因突变频率的影响。匹配队列分析用于确定组织学特异性的种族相关突变，包括黑人患者和亚洲患者的胶质瘤和膀胱癌中 TERT 启动子突变增加，以及亚洲患者和黑人患者中多个癌症类型的 DNA 修复途径基因和 SWI/SNF 染色质复合物亚基的突变频率降低。致癌基因中可操作突变的分布也是种族特异性的，表明靶向治疗可能对不同种族群体产生不同的影响。下采样分析表明，更大的样本量可能会发现更多的种族相关突变。这些结果提供了一个资源，以了解不同种族之间的癌症基因组差异，这可能为生物标志物试验中的临床研究和患者招募策略的设计提供信息。
