Mouse study shows liver tumors can form without detectable driver mutations
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Researchers at the Institute of Science Tokyo report in Communications Biology that hepatocellular carcinoma can arise without canonical driver gene mutations. Using a mouse mosaic model with activated YAP1, they traced tumor formation to the YAP1-TEAD-TET1 axis, which drives DNA demethylation that activates multiple oncogenes. Inhibiting TET1 reduced tumor formation, and human data from Fontan-associated liver disease support the pathway's relevance to human disease. The findings point to an epigenetic route to liver cancer that mutation-focused screening and therapy may miss, and they position TET1 as a potential therapeutic target. Questions still open include how the pathway behaves across other liver cancer settings and whether TET1 inhibition can be translated into clinical benefit. The paper's DOI is 10.1038/s42003-026-10882-w.
Written by a model from the reports · updated 2 hours ago
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- medicalxpress.comPickLiver tumors form without detectable driver mutations in mice, revealing epigenetic route
A team at Institute of Science Tokyo built a mosaic mouse model activating YAP1 and found that hepatocellular carcinoma can form without canonical driver gene mutations, with the YAP1-TEAD-TET1 axis mediating DNA demethylation that activates multiple oncogenes. Suppressing TET1 reduced tumor formation, and human Fontan-associated liver disease data support the pathway's relevance. The study appears in Communications Biology (DOI: 10.1038/s42003-026-10882-w).
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