Prognostic Implications of and Relationship between CpG Island Hypermethylation and Repetitive DNA Hypomethylation in Hepatocellular Carcinoma
HS Lee, BH Kim, NY Cho, SH Shin, JJ Jang, KS Suh, GH Kang. Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
Background: This study aims to determine the relationship between CpG island DNA hypermethylation and global genomic DNA hypomethylation and their prognostic implications in hepatocellular carcinoma (HCC). The association of DNA methylation changes with clinicopathologic factors and the chronological ordering of DNA methylation changes along multistep hepatocarcinogenesis were also assessed.
Design: HCC (n=20) and non-neoplastic liver samples (n=72) were analyzed for their methylation status at 41 CpG island loci and three repetitive DNA elements (LINE-1, ALU, and SAT2) using MethyLight or combined bisulfite restriction analysis. After selection of 19 CpG island loci showing cancer-specific DNA methylation, another set of 99 HCC samples were analyzed for these loci.
Results: The number of methylated genes in HCC was significantly higher in HCC patients with a cirrhotic liver than in HCC patients with a non-cirrhotic liver (8.8 vs. 6.1, P<0.001). HCC from female patients showed a higher number of methylated genes than HCC from male patients (9.9 vs. 7.2, P=0.004). The genes CRABP1 and SYK showed significant association between CpG island hypermethylation and patients' poor survival. SAT2 hypomethylation occurred earlier than LINE-1 or ALU hypomethylation along the multistep hepatocarcinogenesis. Depending on the type of CpG island locus, a direct, inverse, or no relationship between CpG island hypermethylation and repetitive DNA hypomethylation was observed in HCCs.
Conclusions: The varying relationships between hypermethylation of individual CpG island loci and hypomethylation of repetitive elements suggests that they are not mechanically linked. SYK and CRABP1 hypermethylation may serve as useful tumor markers for prognostication of HCC patients.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 171, Tuesday Morning