Characterization of aberrant splicing in pediatric central nervous system tumors reveals <i>CLK1</i> as a candidate oncogenic dependency.

ABSTRACT: Pediatric brain cancer is the leading cause of disease-related mortality in children, and many aggressive tumors still lack effective treatment strategies. We characterized aberrant alternative splicing across pediatric brain tumors, identifying pediatric high-grade gliomas (HGGs) among the most heterogeneous. Annotating these events with UniProt, we identified 11,940 splice events in 5,368 genes leading to potential protein function changes. We discovered CDC-like kinase 1 (CLK1) is aberrantly spliced to favor exon 4 inclusion, resulting in a gain of two phosphorylation sites and subsequent activation. Inhibition of CLK1 with Cirtuvivint significantly decreased both cell viability and proliferation in the pediatric HGG KNS-42 cell line. Morpholino-mediated depletion o

SUBMITTER: Naqvi AS 

PROVIDER: S-EPMC11326178 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature