Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

JFH1-huh7.5.1

ABSTRACT: Genome wide DNA methylation analysis usig two individual huh7.5.1 after HCV-JFH1 infection

ORGANISM(S): Homo sapiens

SUBMITTER: okamoto yasuyuki

PROVIDER: E-MTAB-1473 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Hepatitis virus infection affects DNA methylation in mice with humanized livers.

Okamoto Yasuyuki Y Shinjo Keiko K Shimizu Yasuhiro Y Sano Tsuyoshi T Yamao Kenji K Gao Wentao W Fujii Makiko M Osada Hirotaka H Sekido Yoshitaka Y Murakami Shuko S Tanaka Yasuhito Y Joh Takashi T Sato Shinya S Takahashi Satoru S Wakita Takaji T Zhu Jingde J Issa Jean-Pierre J JP Kondo Yutaka Y

Gastroenterology 20131030 2

<h4>Background & aims</h4>Cells of tumors associated with chronic inflammation frequently have altered patterns of DNA methylation, including hepatocellular carcinomas. Chronic hepatitis has also been associated with aberrant DNA methylation, but little is known about their relationship.<h4>Methods</h4>Pyrosequencing was used to determine the methylation status of cultured Huh7.5.1 hepatoma cells after hepatitis C virus (HCV) infection. We also studied mice with severe combined immunodeficiency ...[more]

PMID: 24184133

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Project description:A large-scale characterization of the methylation states of candidate CpG islands (CGIs) throughout the gastric cancer methylome has not previously been conducted. Genome-wide DNA methylation profiles were compared between 4 metastatic and 4 non-metastatic gastric carcinomas (GCs) and their surgical margins (SMs). The GC genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared to SMs. Differential methylation was observed in CGIs near transcription start sites of 546 genes between GCs and SMs, and 601 genes between metastatic and non-metastatic GCs. From the list of differentially methylated CGIs, 68 candidate genes and 10 known tumor-related genes were selected for further characterization based on their known molecular function using DHPLC. Significant differential methylation was validated in the CGIs of 15 genes between GCs and SMs (Ps<0.05) and confirmed using bisulfite-sequencing. These genes include BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Hypomethylation of CGIs correlated with up-regulation of GFRA1 expression in GCs, while hypermethylation of other genes inactivated their transcription. Most importantly, prevalence of GFRA1, SRF, and ZNF382 methylation alterations were inversely and coordinately associated with GC metastasis and the patients’ overall survival throughout discovery and testing cohorts in China as well as independent validation cohorts in Japan and Korea. In conclusion, methylation changes in the CGIs of 15 genes correlated strongly with GC development. GFRA1 hypomethylation and SRF and ZNF382 hypermethylation are potential synergistic biomarkers for the prediction of GC metastasis. To identify differential methylation of CGIs related to GC development and metastasis, genome-wide DNA methylation changes in 8 pairs of GC and SM samples were analysed using the MCAM assay with a 99K custom-designed Agilent oligonucleotide microarray composed of 99,027 probes targeting 6,177 unique protein-coding genes containing at least two methylation-sensitive/insensitive SmaI/ XmaI restriction sites (CCC|GGG/ C|CmCGGG) as described in Shen et al, PLoS Genet 3, 2023-2036 (2007).

Dataset Information

JFH1-huh7.5.1

Publications

Hepatitis virus infection affects DNA methylation in mice with humanized livers.

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