Chronic liver injury alters driver mutation profiles in hepatocellular carcinoma in mice.

ABSTRACT: Most hepatocellular carcinomas (HCCs) develop in a chronically injured liver, yet the extent to which this microenvironment promotes neoplastic transformation or influences selective pressures for genetic drivers of HCC remains unclear. We sought to determine the impact of hepatic injury in an established mouse model of HCC induced by Sleeping Beauty transposon mutagenesis. Chemically induced chronic liver injury dramatically increased tumor penetrance and significantly altered driver mutation profiles, likely reflecting distinct selective pressures. In addition to established human HCC genes and pathways, we identified several injury-associated candidates that represent promising loci for further study. Among them, we found that FIGN is overexpressed in human HCC and promotes hepatocyte i

SUBMITTER: Riordan JD 

PROVIDER: S-EPMC5826818 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature