Journal Watch: Dr Tu looks back at the most important research articles released in 2018 relating to models and biomarkers of hepatocellular carcinoma.

Wang G, Chow RD, Ye L et al. Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR-mediated direct in vivo screening. Sci. Adv. 4(2), eaao5508 (2018). Multiple putative hepatocellular carcinoma (HCC) driver mutations have been identified using next-generation sequencing, but the majority have not been confirmed in in vivo settings or in combination with each other. Wang et al. describe a high-throughput solution by transducing transgenic mice containing a Cre-dependent Cas9 with hepatocyte-specific adeno-associated virus vectors that encode for Cre recombinase, EGFP and a sgRNA from a library, targeting HCC candidate genes (49 genes drawn from online databases). Indels at target loci were then confirmed and quantified using multiplexed molecular inversion probe sequencing. Within 3 months of transduction, mice developed multifocal GFP-positive HCC, in which significant enrichment of Trp53, Setd2, Cic and Pik3R1 mutations were observed. Several pairs of mutations were significantly enriched, including Cdkn2a and Pten, B2m and Kansl1, and Arid2 and Cdkn2a. This exciting novel HCC model has the potential to confirm thousands of gene candidates identified by sequencing projects.