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.
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.
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.
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.
Published by Elsevier Inc.