Genome wide DNA methylation profiling reveals novel candidate epigenetic gatekeepers in hepatocarcinogenesis

Epigenetic deregulation is a critical event in human malignancies. Besides mutations in TERT promoter, found in 20% of dysplastic nodules, little is known about the key molecular alterations driving early hepatocarcinogenesis. The aims of this study were: 1) to analyze DNA methylation changes during the transition from preneoplastic lesions to early hepatocellular carcinoma (HCC), and 2) to identify candidate epigenetic gatekeepers in the transition between dysplasia and early tumors.Methylome profiling was done with Illumina HumanMethylation450 (485,000 CpG, 96% of known CpG islands). We evaluated differentially methylated CpG sites between groups using an F-test. To detect novel epigenetic gatekeepers we defined hypermethylation as a B value higher than 0.5. We profiled 144 fresh-frozen tissues from resection or liver transplant specimens and integrated these data with our previously report on …