Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations.

ABSTRACT: Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC),

SUBMITTER: Dong X 

PROVIDER: S-EPMC11449910 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature