Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns
Yang, Xiaofei2; Gao, Lin2; Zhang, Shihua1
刊名BRIEFINGS IN BIOINFORMATICS
2017-09-01
卷号18期号:5页码:761-773
关键词cancer genomics DNA-methylation pan-cancer study bioinformatics
ISSN号1467-5463
DOI10.1093/bib/bbw063
英文摘要Abnormal DNA methylation is an important epigenetic regulator involving tumorigenesis. Deciphering cancer common and specific DNA methylation patterns is essential for us to understand the mechanisms of tumor development. The Cancer Genome Atlas (TCGA) project provides a large number of samples of different cancers that enable a pan-cancer study of DNA methylation possible. Here we investigate cancer common and specific DNA methylation patterns among 5480 DNA methylation profiles of 15 cancer types from TCGA. We first define differentially methylated CpG sites (DMCs) in each cancer and then identify 5450 hyper- and 4433 hypomethylated pan-cancer DMCs (PDMCs). Intriguingly, three adjacent hyperme-thylated PDMC constitute an enhancer region, which potentially regulates two tumor suppressor genes BVES and PRDM1 negatively. Moreover, we identify six distinct motif clusters, which are enriched in hyper- or hypomethylated PDMCs and are associated with several well-known cancer hallmarks. We also observe that PDMCs relate to distinct transcriptional groups. Additionally, 55 hypermethylated and 7 hypomethylated PDMCs are significantly associated with patient survival. Lastly, we find that cancer-specific DMCs are enriched in known cancer genes and cell-type-specific super-enhancers. In summary, this study provides a comprehensive investigation and reveals meaningful cancer common and specific DNA methylation patterns.
资助项目National Natural Science Foundation of China[61379092] ; National Natural Science Foundation of China[61422309] ; National Natural Science Foundation of China[61532014] ; National Natural Science Foundation of China[91530113] ; National Natural Science Foundation of China[61432010] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDB13040600] ; Outstanding Young Scientist Program of CAS ; Fundamental Research Funds for the Central Universities[BDZ021404] ; Key Laboratory of Random Complex Structures and Data Science at CAS
WOS研究方向Biochemistry & Molecular Biology ; Mathematical & Computational Biology
语种英语
出版者OXFORD UNIV PRESS
WOS记录号WOS:000411516400005
内容类型期刊论文
源URL[http://ir.amss.ac.cn/handle/2S8OKBNM/26671]  
专题应用数学研究所
通讯作者Gao, Lin; Zhang, Shihua
作者单位1.Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Beijing 100190, Peoples R China
2.Xidian Univ, Xian, Shaanxi, Peoples R China
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GB/T 7714
Yang, Xiaofei,Gao, Lin,Zhang, Shihua. Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns[J]. BRIEFINGS IN BIOINFORMATICS,2017,18(5):761-773.
APA Yang, Xiaofei,Gao, Lin,&Zhang, Shihua.(2017).Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns.BRIEFINGS IN BIOINFORMATICS,18(5),761-773.
MLA Yang, Xiaofei,et al."Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns".BRIEFINGS IN BIOINFORMATICS 18.5(2017):761-773.
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