Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns

doi:10.1093/bib/bbw063

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	Comparative pan-cancer DNA methylation analysis reveals cancer common and specific patterns
	Yang, Xiaofei 2; Gao, Lin 2; Zhang, Shihua1
	2017-09-01
发表期刊	BRIEFINGS IN BIOINFORMATICS
ISSN	1467-5463
卷号	18 期号:5 页码:761-773
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.
关键词	cancer genomics DNA-methylation pan-cancer study bioinformatics
DOI	10.1093/bib/bbw063
语种	英语
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
WOS类目	Biochemical Research Methods ; Mathematical & Computational Biology
WOS记录号	WOS:000411516400005
出版者	OXFORD UNIV PRESS
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/26672
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
推荐引用方式 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.