40 (PB030) - Genome-wide mapping of cancer dependency and genetic modifiers of chemotherapy using a high-risk hepatoblastoma genetic model

Abstract

A lack of genetic models hampers our understanding of hepatoblastoma pathogenesis and the development of new therapies for this neoplasm. We have developed a liver-specific MYC-driven murine model that faithfully recapitulates the pathological features of human hepatoblastoma, with transcriptomics resembling the high-risk gene signatures of the human disease. Single-cell RNA-sequencing and spatial transcriptomics identified distinct subpopulations of hepatoblastoma cells. After deriving cell lines from the mouse model, we mapped the cancer dependency genes using CRISPR-Cas9 screening and identified druggable targets conserved in human hepatoblastoma.