UNLABELLED: Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA before HCC diagnosis. To identify, with a genome-wide approach, additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent nontumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays (Illumina, Inc., San Diego, CA) that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor, compared to nontumor tissues. Array data were validated with pyrosequencing in a subset of five of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37%-63% of cases had detectable hypermethylated DNA (≥ 5% methylation) for these five genes individually. At least one of these genes was hypermethylated in 87% of the cases, suggesting that measurement of DNA methylation in plasma samples is feasible. CONCLUSION: The panel of methylated genes indentified in the current study will be further tested in a large cohort of prospectively collected samples to determine their utility as early biomarkers of HCC.
UNLABELLED: Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA before HCC diagnosis. To identify, with a genome-wide approach, additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent nontumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays (Illumina, Inc., San Diego, CA) that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor, compared to nontumor tissues. Array data were validated with pyrosequencing in a subset of five of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37%-63% of cases had detectable hypermethylated DNA (≥ 5% methylation) for these five genes individually. At least one of these genes was hypermethylated in 87% of the cases, suggesting that measurement of DNA methylation in plasma samples is feasible. CONCLUSION: The panel of methylated genes indentified in the current study will be further tested in a large cohort of prospectively collected samples to determine their utility as early biomarkers of HCC.
Authors: Y J Zhang; C J Chen; C S Lee; B Haghighi; G Y Yang; L W Wang; M Feitelson; R Santella Journal: Carcinogenesis Date: 1991-12 Impact factor: 4.944
Authors: Jan Harder; Oliver G Opitz; Jan Brabender; Manfred Olschewski; Hubert E Blum; Shuji Nomoto; Henning Usadel Journal: Int J Cancer Date: 2008-06-15 Impact factor: 7.396
Authors: Hang Su; Jing Zhao; Yujuan Xiong; Teng Xu; Fan Zhou; Yunfei Yuan; Ying Zhang; Shi-Mei Zhuang Journal: Mutat Res Date: 2008-02-14 Impact factor: 2.433
Authors: Min-Ae Song; Sandi A Kwee; Maarit Tiirikainen; Brenda Y Hernandez; Gordon Okimoto; Naoky C Tsai; Linda L Wong; Herbert Yu Journal: Epigenetics Date: 2016-06-01 Impact factor: 4.528
Authors: Jing Shen; Shuang Wang; Yu-Jing Zhang; Hui-Chen Wu; Muhammad G Kibriya; Farzana Jasmine; Habibul Ahsan; David P H Wu; Abby B Siegel; Helen Remotti; Regina M Santella Journal: Epigenetics Date: 2012-12-03 Impact factor: 4.528