The Alb-R26Met setting as an “open” predisposition model recapitulates several features of HCC patients: the molecular heterogeneity, the primary resistance to drugs used in the clinic, the temporal heterogeneity of tumour onset [29], and the enrichment in genes both overexpressed and hypermethylated in gene body CpG islands occurring in 56% of proliferative-progenitor HCC patients [31]. The gene discussed is ALB; the disease is hepatocellular carcinoma.