Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer.

ABSTRACT: Pediatric liver cancers (PLC) comprise diverse diseases affecting infants, children, and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of patients with hepatoblastoma, all before three years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between "hepatocytic," "liver progenitor," and "mesenchymal" molecular subgroups of hepatoblastoma. We showed that during chemotherapy, "liver progenitor" cells accumulated massive loads of cisplatin-induce

SUBMITTER: Hirsch TZ 

PROVIDER: S-EPMC8916021 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature