Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences

Lung cancer is one of the most frequently diagnosed cancers with higher incidence and mortality rates in African-American (AA) men compared to European-American (EA) men. Here, we report high-confidence alternative splicing (AS) events from high-throughput, high-depth total RNA-sequencing of lung tumors and non-tumor adjacent tissues (NATs) from two independent cohorts of patients with adenocarcinoma and squamous cell carcinoma. We uncover tumor subtype- and population-specific AS events different between AAs and EAs, associated with oncogenic signaling pathways, cell surface proteins, and cancer driver genes. We highlight significant AS events in SYNE2 specific to LUAD in both populations as well as those in CD44 from EAs and TMBIM6 from AAs specific to LUAD. Our large survey of lung tumors presents a rich data resource that can help uncover new therapeutic vulnerabilities that potentially advance health equity.