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Semin Liver Dis. 2019 May;39(2):261-274. doi: 10.1055/s-0039-1678725. Epub 2019 Mar 25.

Liver Cancer Gene Discovery Using Gene Targeting, Sleeping Beauty, and CRISPR/Cas9.

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Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Aix Marseille Univ, CNRS, Developmental Biology Institute of Marseille (IBDM) UMR 7288, Parc Scientifique de Luminy, Marseille, France.
Penn NCI Physical Sciences in Oncology Center PSOC@Penn and the NSF Center for Engineering MechanoBiology, University of Pennsylvania, Philadelphia, Pennsylvania.


Hepatocellular carcinoma (HCC) is a devastating and prevalent cancer with limited treatment options. Technological advances have enabled genetic screens to be employed in HCC model systems to characterize genes regulating tumor initiation and growth. Relative to traditional methods for studying cancer biology, such as candidate gene approaches or expression analysis, genetic screens have several advantages: they are unbiased, with no a priori selection; can directly annotate gene function; and can uncover gene-gene interactions. In HCC, three main types of screens have been conducted and are reviewed here: (1) transposon-based mutagenesis screens, (2) knockdown screens using RNA interference (RNAi) or the CRISPR/Cas9 system, and (3) overexpression screens using CRISPR activation (CRISPRa) or cDNAs. These methods will be valuable in future genetic screens to delineate the mechanisms underlying drug resistance and to identify new treatments for HCC.


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