Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-03-29

AUTHORS

Masahiro Shitani, Shigeru Sasaki, Noriyuki Akutsu, Hideyasu Takagi, Hiromu Suzuki, Masanori Nojima, Hiroyuki Yamamoto, Takashi Tokino, Koichi Hirata, Kohzoh Imai, Minoru Toyota, Yasuhisa Shinomura

ABSTRACT

Aberrant DNA methylation has been implicated in the development of hepatocellular carcinoma (HCC). Our aim was to clarify its molecular mechanism and to identify useful biomarkers by screening for DNA methylation in HCC. Methylated CpG island amplification coupled with CpG island microarray (MCAM) analysis was carried out to screen for methylated genes in primary HCC specimens [hepatitis B virus (HBV)-positive, n = 4; hepatitis C virus (HCV)-positive, n = 5; HBV/HCV-negative, n = 7]. Bisulfite pyrosequencing was used to analyze the methylation of selected genes and long interspersed nuclear element (LINE)-1 in HCC tissue (n = 57) and noncancerous liver tissue (n = 50) from HCC patients and in HCC cell lines (n = 10). MCAM analysis identified 332, 342, and 259 genes that were methylated in HBV-positive, HCV-positive, and HBV/HCV-negative HCC tissues, respectively. Among these genes, methylation of KLHL35, PAX5, PENK, and SPDYA was significantly higher in HCC tissue than in noncancerous liver tissue, irrespective of the hepatitis virus status. LINE-1 hypomethylation was also prevalent in HCC and correlated positively with KLHL35 and SPDYA methylation. Receiver operating characteristic curve analysis revealed that methylation of the four genes and LINE-1 strongly discriminated between HCC tissue and noncancerous liver tissue. Our data suggest that aberrant hyper- and hypomethylation may contribute to a common pathogenesis mechanism in HCC. Hypermethylation of KLHL35, PAX, PENK, and SDPYA and hypomethylation of LINE-1 could be useful biomarkers for the detection of HCC. More... »

PAGES

1307-1317

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13277-012-0378-3

DOI

http://dx.doi.org/10.1007/s13277-012-0378-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039674334

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22457049


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34 schema:description Aberrant DNA methylation has been implicated in the development of hepatocellular carcinoma (HCC). Our aim was to clarify its molecular mechanism and to identify useful biomarkers by screening for DNA methylation in HCC. Methylated CpG island amplification coupled with CpG island microarray (MCAM) analysis was carried out to screen for methylated genes in primary HCC specimens [hepatitis B virus (HBV)-positive, n = 4; hepatitis C virus (HCV)-positive, n = 5; HBV/HCV-negative, n = 7]. Bisulfite pyrosequencing was used to analyze the methylation of selected genes and long interspersed nuclear element (LINE)-1 in HCC tissue (n = 57) and noncancerous liver tissue (n = 50) from HCC patients and in HCC cell lines (n = 10). MCAM analysis identified 332, 342, and 259 genes that were methylated in HBV-positive, HCV-positive, and HBV/HCV-negative HCC tissues, respectively. Among these genes, methylation of KLHL35, PAX5, PENK, and SPDYA was significantly higher in HCC tissue than in noncancerous liver tissue, irrespective of the hepatitis virus status. LINE-1 hypomethylation was also prevalent in HCC and correlated positively with KLHL35 and SPDYA methylation. Receiver operating characteristic curve analysis revealed that methylation of the four genes and LINE-1 strongly discriminated between HCC tissue and noncancerous liver tissue. Our data suggest that aberrant hyper- and hypomethylation may contribute to a common pathogenesis mechanism in HCC. Hypermethylation of KLHL35, PAX, PENK, and SDPYA and hypomethylation of LINE-1 could be useful biomarkers for the detection of HCC.
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40 schema:keywords CpG island amplification
41 CpG island microarray analysis
42 DNA methylation
43 HBV
44 HCC cell lines
45 HCC patients
46 HCC tissues
47 HCV
48 LINE-1
49 LINE-1 hypomethylation
50 Methylated CpG Island Amplification
51 PAX5
52 PENK
53 Pax
54 aberrant DNA methylation
55 aberrant hyper
56 aim
57 amplification
58 analysis
59 biomarkers
60 bisulfite pyrosequencing
61 cancer-related genes
62 carcinoma
63 cell lines
64 characteristic curve analysis
65 curve analysis
66 data
67 detection
68 detection of HCC
69 development
70 elements
71 genes
72 genome-wide analysis
73 hepatitis virus status
74 hepatocellular carcinoma
75 hyper
76 hypermethylation
77 hypomethylation
78 lines
79 liver tissue
80 mechanism
81 methylation
82 microarray analysis
83 molecular mechanisms
84 noncancerous liver tissues
85 novel cancer-related gene
86 nuclear elements
87 pathogenesis mechanisms
88 patients
89 primary hepatocellular carcinoma
90 pyrosequencing
91 receiver
92 screen
93 status
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96 virus status
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