Table 1.

Summary of comprehensive analyses of DNA methylation in human HCC

Year	Methods (CpG sites analyzed]	Number of cases analyzed	Results	Reference
2008	MCAMs (6,458 CpG islands] Pyrosequence	38 cases of HCC	Methylation events were classified into 4 groups according to the progression of methylation from normal liver to HCC	Gao et al. [11]
2009	BAMCA	25 cases of HCC 26 of normal liver	Methylation profile of HCC was associated with overall and recurrence-free survival after hepatectomy	Arai et al.[19]
2010	GoldenGate methylation assaya (1,505 CpG sites]	38 cases of HCC	Methylation status of 10 CpGs predicts survival of HCC patients	Hernandez-Vargas et al.[24]
2011	BAMCA Pyrosequence (203 CpG sites]	34 cases of HCC 45 of normal liver	Methylation status of background liver was associated with survival in patients who underwent liver resection	Nagashio et al.[25]
2011	HM27 BeadChip (27,578 CpG sites] COBRA (17 CpG sites]	13 cases of HCC	Methylation was analyzed in HCC cells isolated from HBV-related HCC tissues and 7 potential TSGs were identified	Tao et al.,[20]
2012	COBRA (27 genes or CpG sites]	177 cases of HCC 128 cases of hepatitis C	Methylation of 8 TSGs was identified as driver alterations for HCC through the analysis of early HCC and chronic hepatitis C without any history of HCC	Nishida et al.[12]
2012	HM27 BeadChip (27,578 CpGs] Pyrosequence (24 CpG sites]	62 cases of HCC	Five methylated genes were identified from the serum, which could constitute a potential tumor marker of HCC	Shen et al.[26]
2012	HM27 BeadChip (27,578 CpG sites]	62 cases of HCC	Several miRs showing abnormal methylation and their host genes were identified	Shen et al.[5]
2012	MeDIP-microarray (27,800 CpG islands]	162 cases of HCC	Eleven potential TSGs were reported through the MeDIP- microarray and pharmacological unmasking analyses. Functional analyses of MZB1 were performed	Matsumura et al.[22]
2012	HM27 BeadChip (27,578 CpG sites]	12 cases of HCC, 15 cases of liver cirrhosis	Methylation differences among HCC, liver cirrhosis, and normal liver were reported. In HCC, many methylated genes were identified as a target of PRC2 in embryonic stem cells	Ammerpohl et al.[15]
2012	HM27 BeadChip (27,578 CpG sites]	63 cases of HCC	Methylation, chromosomal alteration, and epigenetically silenced genes were analyzed comprehensively using BeadChip, array CGH, and expression arrays accompanied by pharmacological unmasking	Neumann et al.[16]
2013	HM450 BeadChip (485,577 CpG sites]	66 cases of HCC	Genome-wide analyses of hypermethylated and hypomethylated regions in HCC using HM450 BeadChip	Shen et al.[17]
2013	HM450 BeadChip (485,577 CpG sites]	45 cases of NAFLD	Methylation differences between mild and advanced NAFLD were reported	Murphy et al.[10]
2013	HM27 BeadChip (27,578 CpG sites]	71 cases of HCV-related HCC	Thirteen potential TSGs were reported using comprehensive methylation and expression analyses accompanied by pharmacological unmasking methods	Revill K et al.[23]
2013	HM450 BeadChip (485,577 CpG sites]	27 cases of HCC	Genome-wide analyses of hypermethylated and hypomethylated regions in HCC using HM450 BeadChip	Song et al.[18]

a=Illumina GoldenGate methylation assay using BeadArray technology. MCAMs=methylated CpG island amplification microarrays; BAMCA=bacterial artificial chromosome array-based methylated CpG island amplification; HM27=Illumina Bead Array, HumanMethylation27 BeadChip; CGH=comparative genomic hybridization; COBRA=combined bisulfite restriction analysis; MeDIP-microarray=methylated DNA immunoprecipitation-microarray analysis; HM450=Illumina Bead Array, HumanMethylation450 BeadChip.