Cells that have undergone mutational ablation of the carboxy-terminal half of SPRTN or single amino acid substitution of a tyrosine to cysteine at position 117 such as those identified in the Ruijs-Aalfs syndrome probands, are compromised for proteolytic activity and are sensitive to DPC-inducing agents. The gene discussed is SPRTN; the disease is progeroid features-hepatocellular carcinoma predisposition syndrome.