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 t-test 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.
BACKGROUND: Global genomic DNA hypomethylation is a feature of genomic DNA derived from solid and hematologic tumors in animal models and humancarcinogenesis. 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 cancerpatients 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 t-test 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.
Authors: Julia Sauer; Hyeran Jang; Ella M Zimmerly; Kyong-Chol Kim; Zhenhua Liu; Aurelie Chanson; Donald E Smith; Joel B Mason; Simonetta Friso; Sang-Woon Choi Journal: Br J Nutr Date: 2010-03-08 Impact factor: 3.718
Authors: Igor P Pogribny; Volodymyr P Tryndyak; Anna Boureiko; Stepan Melnyk; Tetyana V Bagnyukova; Beverly Montgomery; Ivan Rusyn Journal: Mutat Res Date: 2008-07-01 Impact factor: 2.433
Authors: Manik Vohra; Prabha Adhikari; Sydney C D' Souza; Shivashankar K Nagri; Shashikiran Umakanth; Kapaettu Satyamoorthy; Padmalatha S Rai Journal: Lab Invest Date: 2020-04-01 Impact factor: 5.662