Relationship Between Dna Methylation Of Tet Genes And Levels Of 5-Methyl-Cytosine And 5-Hydroxymethyl-Cytosine In Hepatocellular Carcinoma

Long-term survival after hepatocellular carcinoma (HCC) diagnosis has clearly improved as a result of treatment by means of a liver transplant. However, a large number of cases do not meet the transplant criteria and undergo resection. In these patients, loss of global DNA hydroxymethylation has been linked to worse prognosis, but no association has been found in transplant patients. Differential epigenetic processing is a possible reason for this, and has not been previously explored. The process of DNA demethylation is mediated by the family of ten-eleven translocation (TET) proteins, that catalyze the conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). There are three different TET protein variants: TET1, TET2 and TET3. Studies have shown that expression of at least TET1 is epigenetically regulated. In this study we investigated the association between DNA methylation of TET genes and global DNA methylation and hydroxymethylation in 66 tumor (T) and non-tumor (NT) paired samples of individuals treated at Columbia Presbyterian Medical Center in New York. Levels of 5mC and 5hmC were determined by UPLC/MS/MS, and DNA methylation of the TET promoters was obtained from Illumina Infinium 450k CpG array data. Mean levels of 5mC (T = 3.15±0.49% vs. NT = 3.80±0.12% (p Citation Format: Lissette Delgado-Cruzata, Hui-Chen Wu, Jin Shen, Tiffany Thomas, Abby B. Siegel, Yu-Jing Zhang, Abhishek Goyal, Christine C. Hsu, Helen E. Remotti, Regina M. Santella. Relationship between DNA methylation of TET genes and levels of 5-methyl-cytosine and 5-hydroxymethyl-cytosine in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4439.