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Status |
Public on May 05, 2015 |
Title |
DNA methylation profiles in alcohol-associated hepatocellular carcinoma |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by array
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Summary |
Alcohol is a major risk factor for hepatocellular carcinoma (HCC) although the mechanisms underlying the alcohol-related liver carcinogenesis are still poorly understood. Alcohol is known to increase hepatocarcinogenesis possibly by inducing aberrant DNA methylation through the reduced provision of methyl groups within the hepatic one-carbon metabolism. Whether the epigenetically-regulated pathways in alcohol-associated HCC can be reversible or modifiable by nutritional factors is unknown. The aim of the present study was to investigate the genome wide promoter DNA methylation profiles along with array-based, gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients the methylation status and transcriptional levels of all annotated genes were compared by analyzing HCC tissue and the cancer-free surrounding liver tissue, following curative surgery. After merging both the DNA methylation and gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced and 56 hypomethylated-repressed genes. A number of potentially novel candidate tumor-suppressor genes (FAM107A, IGFALS, MT1G, MT1H, RNF180) demonstrated promoter hypermethylation and transcriptional repression in alcohol-associated HCC. Notably, promoter DNA methylation appeared as the regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolic pathway (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16) and SHMT1, a key gene within one-carbon metabolism. A genome-wide DNA methylation approach linked up with array-based gene expression profiles allowed identifying a number of novel, epigenetically-regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically-regulated through promoter DNA methylation in alcohol-associated hepatocarcinogenesis.
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Overall design |
16 samples (8 control samples from non-neoplastic liver tissue, 8 test samples from hepatocellular carcinoma) from 8 patients affected from hepatocellular carcinoma were analyzed.
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Contributor(s) |
Udali S, Guarini P |
Citation(s) |
25945129 |
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Submission date |
Jul 09, 2014 |
Last update date |
Aug 05, 2015 |
Contact name |
Alberto Ferrarini |
E-mail(s) |
alberto.ferrarini@univr.it
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Phone |
+39-045-802-7058
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Organization name |
University of Verona
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Department |
Scientific and Technological Department
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Lab |
Plant Functional Genomics Centre
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Street address |
Strada le Grazie, 15
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City |
Verona |
State/province |
Veneto |
ZIP/Postal code |
37134 |
Country |
Italy |
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Platforms (1) |
GPL15160 |
NimbleGen Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Arrays (090618_HG18_CpG_Refseq_Prom_MeDIP) |
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Samples (16)
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This SubSeries is part of SuperSeries: |
GSE59261 |
Expression and DNA methylation profiles in alcohol-associated hepatocellular carcinoma |
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Relations |
BioProject |
PRJNA254824 |