期刊
MOLECULAR CARCINOGENESIS
卷 54, 期 3, 页码 178-188出版社
WILEY-BLACKWELL
DOI: 10.1002/mc.22085
关键词
epigenetics; DNA methylation; squamous cell carcinoma; mouse model
资金
- National Institute of Environmental Health Services [ES012249]
- Roswell Park Alliance Foundation
- NCI Cancer Center
- Roswell Park Cancer Institute [CA016156]
- Academic Frontier Project for Project for Private Universities matching fund subsidy from MEXT
- MEXT KAKENHI [23300344, 24591637]
- Grants-in-Aid for Scientific Research [24591637, 23300344, 26290060] Funding Source: KAKEN
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. (c) 2013 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据