CMTR2 mutation in lung adenocarcinoma alters RNA alternative splicing and confers therapeutic vulnerability

RNA splicing dysregulation is emerging as a hallmark of cancer. This study investigates the impact of CMTR2 (Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 2) mutations on RNA splicing in lung adenocarcinoma (LADC). We performed RNA sequencing on multiple cell lines, including CRISPR-Cas9-induced CMTR2 knockout cells and their controls, naturally occurring CMTR2-mutant cells, and their responses to Indisulam treatment versus DMSO control. This dataset aims to elucidate CMTR2 mutation's role in RNA splicing regulation and its potential as a therapeutic target. The study unveils a novel correlation between RNA cap methyltransferase dysfunction and splicing abnormalities, with implications for therapeutic stratification in LADC. Our findings provide insights into RNA splicing dysregulation in cancer and potential avenues for targeted therapies using RNA splicing modulators and immune checkpoint blockade.