1. Comparative DNA methylome analysis of endometrial carcinoma reveals complex and distinct deregulation of cancer promoters and enhancers
- Author
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Bo Zhang, Ting Wang, Xiao Yun Xing, Jing Li, Katherine B. Chiappinelli, Paul J. Goodfellow, David G. Mutch, Rebecca F. Lowdon, Nan Lin, Vasavi Sundaram, Ian S. Hagemann, Baoxue Zhang, and Yan Zhou
- Subjects
Kruppel-Like Transcription Factors ,Biology ,Polymorphism, Single Nucleotide ,Aldehyde Dehydrogenase 1 Family ,Kruppel-Like Factor 4 ,Genetics ,Humans ,DNA (Cytosine-5-)-Methyltransferases ,Methylated DNA immunoprecipitation ,Promoter Regions, Genetic ,Enhancer ,Adaptor Proteins, Signal Transducing ,Chromosomes, Human, X ,Nuclear Proteins ,Retinal Dehydrogenase ,Promoter ,Sequence Analysis, DNA ,Methylation ,DNA Methylation ,Molecular biology ,Carcinoma, Papillary ,Endometrial Neoplasms ,3. Good health ,Enhancer Elements, Genetic ,Differentially methylated regions ,CpG site ,Uterine Neoplasms ,DNA methylation ,DNA Transposable Elements ,CpG Islands ,Female ,RNA, Long Noncoding ,DNA microarray ,MutL Protein Homolog 1 ,Research Article ,Biotechnology - Abstract
Background Aberrant DNA methylation is a hallmark of many cancers. Classically there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I, and uterine papillary serous carcinoma (UPSC), or Type II. However, the whole genome DNA methylation changes in these two classical types of endometrial cancer is still unknown. Results Here we described complete genome-wide DNA methylome maps of EAC, UPSC, and normal endometrium by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq). We discovered distinct genome-wide DNA methylation patterns in EAC and UPSC: 27,009 and 15,676 recurrent differentially methylated regions (DMRs) were identified respectively, compared with normal endometrium. Over 80% of DMRs were in intergenic and intronic regions. The majority of these DMRs were not interrogated on the commonly used Infinium 450K array platform. Large-scale demethylation of chromosome X was detected in UPSC, accompanied by decreased XIST expression. Importantly, we discovered that the majority of the DMRs harbored promoter or enhancer functions and are specifically associated with genes related to uterine development and disease. Among these, abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs. Conclusions DNA methylation changes are an important signature of endometrial cancer and regulate gene expression by affecting not only proximal promoters but also distal enhancers. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-868) contains supplementary material, which is available to authorized users.
- Published
- 2014
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