Journal article
Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma
PloS one, v 6(11), pp e26799-e26799
2011
PMID: 22073196
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hypermethylation of the promoter of the tumor suppressor gene, adenomatous polyposis coli (APC), occurs in various malignancies, including hepatocellular carcinoma (HCC). However, reports on the specificity of the methylation of the APC gene for HCC have varied. To gain insight into how these variations occur, bisulfite PCR sequencing was performed to analyze the methylation status of both sense and antisense strands of the APC gene in samples of HCC tissue, matched adjacent non-HCC liver tissue, hepatitis, cirrhosis, and normal liver tissues. DNA derived from fetal liver and 12 nonhepatic normal tissue was also examined. These experiments revealed liver-specific, antisense strand-biased CpG methylation of the APC gene and suggested that, although methylation of the antisense strand of the APC gene exists in normal liver and other non-HCC disease liver tissue, methylation of the sense strand of the APC gene occurs predominantly in HCC. To determine the effect of the DNA strand on the specificity of the methylated APC gene as a biomarker for HCC detection, quantitative methylation-specific PCR assays for sense and antisense strand DNA were developed and performed on DNA isolated from HCC (n = 58), matched adjacent non-HCC (n = 58), cirrhosis (n = 41), and hepatitis (n = 39). Receiver operating characteristic curves were constructed. With the cutoff value set at the limit of detection, the specificity of sense and antisense strand methylation was 84% and 43%, respectively, and sensitivity was 67.2% and 72.4%, respectively. This result demonstrated that the identity of the methylated DNA strand impacted the specificity of APC for HCC detection. Interestingly, methylation of the sense strand of APC occurred in 40% of HCCs from patients with serum AFP levels less than 20 ng/mL, suggesting a potential role for APC as a biomarker to complement AFP in HCC screening.
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Details
- Title
- Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma
- Creators
- Surbhi Jain - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of AmericaTing-Tsung ChangJames P HamiltonSelena Y LinYih-Jyh LinAlison A EvansFlorin M SelaruPin-Wen LinShun-Hua ChenTimothy M BlockChi-Tan HuWei SongStephen J MeltzerYing-Hsiu Su
- Publication Details
- PloS one, v 6(11), pp e26799-e26799
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- R01 CA125642 / NCI NIH HHS R01 CA133012 / NCI NIH HHS R01 CA136607 / NCI NIH HHS K08 DK090154 / NIDDK NIH HHS CA133012 / NCI NIH HHS CA085069 / NCI NIH HHS CA146799 / NCI NIH HHS R01 DK087454 / NIDDK NIH HHS U01 CA085069 / NCI NIH HHS R01 CA146799 / NCI NIH HHS DK087454 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Epidemiology and Biostatistics
- Web of Science ID
- WOS:000297154900038
- Scopus ID
- 2-s2.0-80355131962
- Other Identifier
- 991014878085404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology