title: Genome-wide DNA methylation profiles in hepatocellular carcinoma.
abstract: Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA before HCC diagnosis. To identify, with a genome-wide approach, additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent nontumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays (Illumina, Inc., San Diego, CA) that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor, compared to nontumor tissues. Array data were validated with pyrosequencing in a subset of five of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37%-63% of cases had detectable hypermethylated DNA (≥ 5% methylation) for these five genes individually. At least one of these genes was hypermethylated in 87% of the cases, suggesting that measurement of DNA methylation in plasma samples is feasible.
  
  
  CONCLUSIONS
  The panel of methylated genes indentified in the current study will be further tested in a large cohort of prospectively collected samples to determine their utility as early biomarkers of HCC.
authors.affiliation: Department of Environmental Health Sciences, Columbia University, New York, NY 10032, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Maya
authors.initials: M
authors.lastname: Kappil
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Wu
authors.forename: Muhammad G
authors.initials: MG
authors.lastname: Kibriya
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Farzana
authors.initials: F
authors.lastname: Jasmine
authors.forename: Habib
authors.initials: H
authors.lastname: Ahsan
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: Ming-Whei
authors.initials: MW
authors.lastname: Yu
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged