Mutations in the coding regions of TP53 and CTNNB1 affect 25–30% of patients with HCC and, along with low-frequency mutations in some other genes (e.g., AXIN1, ARID2, ARID1A, TSC1/TSC2), define core pathways that are commonly de-regulated in HCC. The gene discussed is TSC1; the disease is hepatocellular carcinoma.