In vivo CRISPR activation screening reveals Chromosome 1q genes VPS72, GBA1, and MRPL9 drive hepatocellular carcinoma.

Background & Aims: Hepatocellular carcinoma (HCC) frequently undergoes regional chromosomal amplification, resulting in elevated gene expression levels. We aimed to elucidate the role of these poorly understood genetic changes by employing CRISPR activation (CRISPRa) screening in mouse livers to identify which genes within these amplified loci are cancer driver genes.

Methods: We used data from The Cancer Genome Atlas (TCGA) to identify that frequently copy number-amplified and upregulated genes all reside on human Chromosomes 1q and 8q.