|
| Status |
Public on Sep 16, 2014 |
| Title |
Epigenetic signatures of alcohol abuse and hepatitis infection during hepatocarcinogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
|
| Summary |
Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC.
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| Overall design |
156 primary tissues and 25 cultured normal and HCC cell lines
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| |
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| Contributor(s) |
Hlady RA, Tiedemann RL, Puszyk W, Roberts LR, Choi J, Liu C, Robertson KD |
| Citation(s) |
25294808 |
| Submission date |
Aug 26, 2014 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Keith D Robertson |
| E-mail(s) |
robertson.keith@mayo.edu
|
| Phone |
507-266-4886
|
| Organization name |
Mayo Clinic
|
| Department |
Molecular Pharmacology & Experimental Therapeutics
|
| Lab |
Epigenetic Etiology of Human Disease Laboratory
|
| Street address |
200 First Street SW, Stabile 12-70
|
| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
|
| Samples (199)
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| Relations |
| BioProject |
PRJNA259521 |
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