Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma

Surbhi Jain, Ting Tsung Chang, James P. Hamilton, Selena Y. Lin, Yih Jyh Lin, Alison A. Evans, Florin M. Selaru, Pin Wen Lin, Shun Hua Chen, Timothy M. Block, Chi Tan Hu, Wei Song, Stephen J. Meltzer, Ying Hsiu Su

研究成果: Article同行評審

25 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號e26799
期刊PloS one
6
發行號11
DOIs
出版狀態Published - 2011 十一月 2

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

指紋 深入研究「Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma」主題。共同形成了獨特的指紋。

引用此