S-adenosyl-methionine treatment selectively block liver cancer cell lines transformation and invasiveness by alterations of cancer- and invasion specific transcriptome and methylome (Bisulfite-Seq). Homo sapiens

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM has been unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated cancer cell lines HepG2 and SKHep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and silenced by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and silences genes in pathways of growth and metastasis that are activated in liver cancer cells. Depletion of two SAM silencing targets similarly reduces cellular transformation and invasiveness. Taken together these data provide a molecular foundation for SAM as an anticancer agent. Overall design: DNA from control and SAM treated 3 cell lines: HepG2, Skhep1 and NorHep was captured using SeqCap Epi CpGiant Enrichment Kit and sequenced