Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors.

ABSTRACT: Our understanding of human hepatocellular carcinoma (HCC) development and progression has been hampered by the lack of in vivo models. We performed a genetic screen of 10 oncogenes and genetic mutations in Fah-ablated immunodeficient mice in which primary human hepatocytes (PHHs) are used to reconstitute a functional human liver. We identified that MYC, TP53^R249S , and KRAS^G12D are highly expressed in induced HCC (iHCC) samples. The overexpression of MYC and TP53^R249S transform PHHs into iHCC in situ, though the addition of KRAS^G12D significantly increases the tumorigenic efficiency. iHCC, which recapitulate the histological architecture and gene expression characteristics of clinical HCC samples, reconstituted HCC after serial transplantations.

SUBMITTER: Jiang Z 

PROVIDER: S-EPMC9171684 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature