Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Cancer Discov. 2022 Nov 2;12(11):2552-2565. doi: 10.1158/2159-8290.CD-22-0312.
Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer genetic ancestry have historically relied upon genome-wide markers, the adaptation to targeted clinical sequencing panels presents an opportunity to incorporate ancestry inference into routine diagnostic workflows. We show that global ancestral contributions and admixture of continental populations can be quantitatively inferred using markers captured by the MSK-IMPACT clinical panel. In a pan-cancer cohort of 45,157 patients, we observed differences by ancestry in the frequency of somatic alterations, recapitulating known associations and revealing novel associations. Despite the comparable overall prevalence of driver alterations by ancestry group, the proportion of patients with clinically actionable alterations was lower for African (30%) compared with European (33%) ancestry. Although this result is largely explained by population-specific cancer subtype differences, it reveals an inequity in the degree to which different populations are served by existing precision oncology interventions.
We performed a comprehensive analysis of ancestral associations with somatic mutations in a real-world pan-cancer cohort, including >5,000 non-European individuals. Using an FDA-authorized tumor sequencing panel and an FDA-recognized oncology knowledge base, we detected differences in the prevalence of clinically actionable alterations, potentially contributing to health care disparities affecting underrepresented populations. This article is highlighted in the In This Issue feature, p. 2483.
准确推断祖源对于确定癌症差异的遗传因素至关重要。尽管历史上推断遗传祖源的方法依赖于全基因组标记，但对靶向临床测序面板的适应为将祖源推断纳入常规诊断工作流程提供了机会。我们表明，使用 MSK-IMPACT 临床面板捕获的标记可以定量推断全球祖源贡献和大陆人群的混合。在一个包含 45157 名患者的泛癌队列中，我们观察到祖源在体细胞改变频率上的差异，重现了已知的关联并揭示了新的关联。尽管祖源群体的驱动性改变的总体患病率相当，但具有临床可操作改变的患者比例对于非洲祖源（30%）来说低于欧洲祖源（33%）。尽管这一结果在很大程度上可以用特定人群的癌症亚型差异来解释，但它揭示了不同人群在接受现有精准肿瘤学干预的程度上存在不平等。
我们在一个真实世界的泛癌队列中对与体细胞突变相关的祖源进行了全面分析，包括>5000 名非欧洲个体。使用 FDA 授权的肿瘤测序面板和 FDA 认可的肿瘤学知识库，我们检测到临床上可操作的改变的患病率存在差异，这可能导致影响代表性不足的人群的医疗保健差异。本文在本期的重点介绍中进行了强调，第 2483 页。
