INTRODUCTION Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. While significant progress has been made profiling the genomic makeup of lung cancer in EAs, AAs continue to be underrepresented. Our objective was to chart the genome-wide landscape of somatic mutations in lung cancer tumors from African Americans. METHODS In this study, we used whole exome sequencing (WES) of 82 tumor and non-involved tissue pairs from AAs. Patients were selected from an ongoing case-control study conducted by the NCI and the University of Maryland. RESULTS Among all samples, we identified 178 significantly mutated genes (P <0.05), five of which passed the threshold for false discovery rate (FDR P<0.1). In lung adenocarcinoma (LUAD) tumors, mutation rates in STK11 (P=0.05) and RB1 (P=0.008) were significantly higher in AA LUAD tumors (25% and 13%, respectively) compared with TCGA EA samples (14% and 4%, respectively). In squamous cell carcinomas, mutation rates in STK11 (P=0.002) were significantly higher among AA (8%) than EA tumors from TCGA (1%). Integrated somatic mutation data with CIBERSORT data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling. CONCLUSIONS While a considerable degree of the somatic mutation landscape is shared between EAs and AAs, discrete differences in mutation frequency in potentially important oncogenes and tumor suppressors exist. Better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities.

中文翻译：

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非裔美国人 NSCLC 的全外显子组分析


简介 在美国，与欧洲裔美国人 (EA) 相比，非洲裔美国人 (AA) 的肺癌发病率更高，尤其是男性。尽管在 EA 地区肺癌基因组构成分析方面取得了重大进展，但 AA 地区的代表性仍然不足。我们的目标是绘制非裔美国人肺癌肿瘤体细胞突变的全基因组图谱。方法 在这项研究中，我们对来自 AA 的 82 个肿瘤和非相关组织对进行了全外显子组测序 (WES)。患者选自国家癌症研究所和马里兰大学正在进行的病例对照研究。结果在所有样本中，我们鉴定出178个显着突变基因（P <0.05），其中5个通过了错误发现率阈值（FDR P<0.1）。在肺腺癌 (LUAD) 肿瘤中，AA LUAD 肿瘤中 STK11 (P=0.05) 和 RB1 (P=0.008) 的突变率显着高于 TCGA EA 样本（14% 和 4 ％， 分别）。在鳞状细胞癌中，AA 中的 STK11 突变率 (P=0.002) (8%) 显着高于 TCGA 中的 EA 肿瘤 (1%)。整合体细胞突变数据与 CIBERSORT 数据分析显示，来自携带 STK11 突变的 AA 的 LUAD 肿瘤已减少干扰素信号传导。结论 虽然 EA 和 AA 之间有相当大程度的体细胞突变情况相同，但潜在重要癌基因和抑癌基因的突变频率存在离散差异。更好地了解 AA 患者肺癌的分子基础并利用这些信息来指导临床干预可能有助于减少差异。