Global DNA hypomethylation in liver cancer cases and controls: A phase I preclinical biomarker development study

Rafael Guerrero-Preston, Regina M. Santella, Adolfo Blanco, Manisha Desai, Maria Berdasco, Mario Fraga

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Global genomic DNA hypomethylation is a feature of genomic DNA derived from solid and hematologic tumors in animal models and human carcinogenesis. Global genomic DNA hypomethylation may be the earliest epigenetic change from a normal to a pre-malignant cell. Objectives: To test if global hypomethylation is a good marker for early detection of cancer we used a novel quantification method of 2′-deoxynucleosides to evaluate DNA methylation in liver cancer cases and controls. Methods: Frozen tissue from liver cancer patients and controls were obtained from the Cooperative Human Tissue Network. DNA was extracted using standard methods. Genomic DNA samples were boiled and treated with nuclease P1 and alkaline phosphatase. Global genomic DNA methylation patterns were obtained using HPLC for fraction separation and mass spectrometry for quantification. A two-sample Rest was performed using Welch's approximation for samples with unequal variances. A Wilcoxon rank sum test was also performed. Results: A global genomic DNA methylation index measuring methylated cytidine relative to global cytidine in the genome was significantly lower (p value = 0.001) for all cases, mean = 2.43 (95% CI, 2.08, 2.78), when compared to controls, mean = 3.55 (95% CI, 3.16, 3.93). Discussion: A correlation between global genomic DNA methylation patterns and type of liver tissue was observed. These results add to the accumulating body of evidence suggesting that global DNA hypomethylation may be a useful biomarker to distinguish between liver cancer cases and controls.

Original languageEnglish (US)
Pages (from-to)223-226
Number of pages4
JournalEpigenetics
Volume2
Issue number4
DOIs
StatePublished - 2007
Externally publishedYes

Keywords

  • Epigenetic approaches to cancer epidemiology
  • Epigenetic biomarkers for early detection
  • Epigenetics of hepatocarcinogenesis
  • Global genomic hypomethylation
  • Molecular cancer screening technology

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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