Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma

Ammerpohl, O., Pratschke, J., Schafmayer, C., Haake, A., Faber, W., von Kampen, O., Brosch, M., Sipos, B., von Schonfels, W., Balschun, K., Rocken, C., Arlt, A., Schniewind, B., Grauholm, J., Kalthoff, H., Neuhaus, P., Stickel, F., Schreiber, S., Becker, T., Siebert, R. and Hampe, J. (2011) Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma Int J Cancer . DOI 10.1002/ijc.26136.

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Supplementary data:

Abstract

Abberrant DNA methylation is one of the hallmarks of cancerogenesis. This study aims to delineate differential DNA methylation in cirrhosis and hepatic cancerogenesis. Patterns of methylation of 27,578 individual CpG loci in twelve hepatocellular carcinomas (HCC), fifteen cirrhotic controls and twelve normal liver samples were investigated using an array-based technology. A supervised principal component analysis (PCA) revealed 167 hypomethylated loci and 100 hypermethylated loci in cirrhosis and HCC as compared to normal controls. Thus, these loci show a "cirrhotic" methylation pattern that is maintained in HCC. In pairwise supervised PCAs between normal liver, cirrhosis and HCC, eight loci were significantly changed in all analyses differentiating the three groups (p<0.0001). Of these, five loci showed highest methylation levels in HCC and lowest in control tissue (LOC55908, CELSR1, CRMP1, GNRH2, ALOX12 and ANGPTL7) while two loci showed the opposite direction of change (SPRR3 and TNFSF15). Genes hypermethylated between normal liver to cirrhosis which maintain this methylation pattern during the development of HCC are depleted for CpG islands, high CpG content promoters and polycomb repressive complex 2 (PRC2) targets in embryonic stem cells. In contrast, genes selectively hypermethylated in HCC as compared to non malignant samples showed an enrichment of CpG islands, high CpG content promoters and PRC2 target genes (p<0.0001). Cirrhosis and hepatocellular carcinoma show distinct patterns of differential methylation with regards to promoter structure, PRC2 targets and CpG islands.

Document Type: Article
Additional Information: Journal article International journal of cancer. Journal international du cancer Int J Cancer. 2011 Apr 15. doi: 10.1002/ijc.26136.
Research affiliation: Kiel University
Refereed: Yes
DOI etc.: 10.1002/ijc.26136
ISSN: 1097-0215 (Electronic) 0020-7136 (Linking)
Date Deposited: 01 Nov 2012 05:07
Last Modified: 23 Jan 2013 10:04
URI: http://eprints.uni-kiel.de/id/eprint/16670

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