Liver tumors form without detectable driver mutations in mice, revealing epigenetic route

A team at Institute of Science Tokyo built a mouse mosaic model activating YAP1 and showed, in Communications Biology, that hepatocellular carcinoma can form without canonical driver gene mutations, via YAP1-TEAD-TET1 axis-mediated DNA demethylation activating multiple oncogenes. Inhibiting TET1 reduced tumor formation, and human Fontan-associated liver disease data support the pathway's relevance. DOI: 10.1038/s42003-026-10882-w.