Pan-cancer analysis reveals widespread genomic alterations and context-specific dependencies across 33 tumor types, highlighting therapeutic vulnerabilities in RHO GTPase signaling.
Key Points
To comprehensively characterize the genomic mutations, expression signatures, and functional dependencies of RHO GTPase pathway components across diverse human cancers.
Analyzed genomic and transcriptomic profiles of 484 RHO GTPase-related genes across more than 10,000 tumor samples representing 33 tumor types from The Cancer Genome Atlas.
Integrated genome-wide functional dependency screen data from over 1,000 gene-edited cancer cell lines with co-expression and gene set enrichment analyses.
Positively selected mutations were identified in both established and uncharacterized RHO pathway genes, accompanied by widespread, tumor-specific differential expression and copy number alterations.
Transcriptional profiling revealed coordinated gene expression programs tied to cancer hallmarks such as cell motility, extracellular matrix remodeling, survival, and immune modulation.
Functional dependency screening identified selective, context-dependent vulnerabilities linked to specific deregulated RHO GTPase pathway members across tumor lineages.