title: Genome-wide screening of aberrant DNA methylation which associated with gene expression in mouse skin cancers.
abstract: Epigenetic alteration of genomic DNA is a common and key process in carcinogenesis. There is considerable evidence indicating that some of the somatic alterations occurring during carcinogenesis in humans also involve the same processes as those observed in mice. Therefore, we analyzed mouse skin cancer tissues induced by the 2-stage carcinogenesis model to identify skin tumor-specific differentially methylated regions (ST-DMRs) during the multistep carcinogenesis process. We have previously identified ST-DMRs using the restriction landmark genomic scanning (RLGS) technique and reported that some of the mouse ST-DMRs were also epigenetically modified in human cancers, such as melanoma, neuroblastoma, and brain tumor. These results encouraged us to pursue global methylation screening in mouse skin carcinogenesis. Using the methylated DNA immunoprecipitation (MeDIP) method combined with the NimbleGen promoter plus CpG island (CpGi) array, we identified 615 ST-DMRs. In combination with global gene expression analysis, 91 of these ST-DMRs were shown to be located on or around the genes differentially expressed between normal skin and tumor tissues, including a candidate human tumor suppressor gene Tfap2e. As observed in human colorectal cancers, Tfap2e was methylated at a CpGi located in intron 3 and downregulated in skin tumors. Our results identified aberrant methylated regions that were associated with gene expression regulation during carcinogenesis, which may indicate critical genetic regions also involved in human carcinogenesis. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan; Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Srimoyee
authors.initials: S
authors.lastname: Ghosh
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.forename: Evan
authors.initials: E
authors.lastname: Morien
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D019175:DNA Methylation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010212:Papilloma / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D050656:Transcription Factor AP-2 / Q000235:genetics*
chemical_list: D004791:Enzyme Inhibitors; C493680:TFAP2E protein, human; D050656:Transcription Factor AP-2; D015127:9,10-Dimethyl-1,2-benzanthracene; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate
keywords: DNA methylation; epigenetics; mouse model; squamous cell carcinoma