Distinct Functional Patterns of Gene Promoter Hypomethylation and Hypermethylation in Cancer Genomes 英文参考文献.docVIP

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Distinct Functional Patterns of Gene Promoter Hypomethylation and Hypermethylation in Cancer Genomes 英文参考文献.doc

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Distinct Functional Patterns of Gene Promoter Hypomethylation and Hypermethylation in Cancer Genomes 英文参考文献

DistinctFunctionalPatternsofGenePromoter HypomethylationandHypermethylationinCancer Genomes XiaopeiShen1,ZhengHe1,HongdongLi1,ChenYao1,YangZhang1,LangHe1,ShanLi1,JianHuang1, ZhengGuo1,2 * 1Bioinformatics Centre, School of Life Science, University of Electronic Science and Technology of China, Chengdu, China, 2College of Bioinformatics Science and Technology,HarbinMedicalUniversity,Harbin,China Abstract Background: Aberrant DNA methylation plays important roles in carcinogenesis. However, the functional significance of genome-widehypermethylationandhypomethylationofgenepromotersincarcinogenesiscurrentlyremainunclear. PrincipalFindings:Basedongenome-widemethylationdataforfivecancertypes,weshowedthatgeneswithpromoter hypermethylation were highly consistent in function across different cancer types, and so were genes with promoter hypomethylation.Functionsrelatedto‘‘developmentalprocesses’’and‘‘regulationofbiologyprocesses’’weresignificantly enrichedwithhypermethylatedgenesbutweredepletedofhypomethylatedgenes.Incontrast,functionsrelatedto‘‘cell killing’’and‘‘responsetostimulus’’,includingimmuneandinflammatoryresponse,wereassociatedwithanenrichmentof hypomethylatedgenesanddepletionofhypermethylatedgenes.Wealsoobservedthatsomefamiliesofcytokinessecreted by immune cells, such as IL10 family cytokines and chemokines, tended to be hypomethylated in various cancer types. These results provide new hints for understanding the distinct functional roles of genome-wide hypermethylation and hypomethylationofgenepromotersincarcinogenesis. Conclusions: Genes with promoter hypermethylation and hypomethylation are highly consistent in function across differentcancertypes,respectively,butthesetwogroupsofgenestendtobeenrichedindifferentfunctionsassociated withcancer.Especially,wespeculatethathypomethylationofgenepromotersmayplayrolesininducingimmunityand inflammation disorders in precancerous conditions, which may provide hints for improving epigenetic therapy and immunotherapyofcancer