Genome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer 英文参考文献.docVIP

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Genome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer 英文参考文献.doc

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Genome-Scale Discovery of DNA-Methylation Biomarkers for Blood-Based Detection of Colorectal Cancer 英文参考文献

Genome-ScaleDiscoveryofDNA-MethylationBiomarkers forBlood-BasedDetectionofColorectalCancer ChristopherP.E.Lange1,4,MihaelaCampan6,ToshinoriHinoue8,RoderickF.Schmitz1,AndreaE.vander Meulen-deJong5,HildeSlingerland5,PeterJ.M.J.Kok2,CornelisM.vanDijk3,DanielJ.Weisenberger8, HuiShen8,RobertusA.E.M.Tollenaar4,PeterW.Laird6,7,8* 1Department of Surgery, Groene Hart Hospital, Gouda, The Netherlands, 2Department of Clinical Chemistry, Groene Hart Hospital, Gouda, The Netherlands, 3Department of Pathology, Groene Hart Hospital, Gouda, The Netherlands, 4Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands, 5Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands, 6Department of Surgery, University of Southern California, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America, 7Department of Biochemistry and MolecularBiology,UniversityofSouthernCalifornia,KeckSchoolofMedicine,USC/NorrisComprehensiveCancerCenter,LosAngeles,California,UnitedStatesofAmerica, 8USCEpigenomeCenter,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica Abstract Background:Thereisanincreasingdemandforaccuratebiomarkersforearlynon-invasivecolorectalcancerdetection.We employed a genome-scale marker discovery method to identify and verify candidate DNA methylation biomarkers for blood-baseddetectionofcolorectalcancer. Methodology/PrincipalFindings:WeusedDNAmethylationdatafrom711colorectaltumors,53matchedadjacent-normal colonictissuesamples,286healthybloodsamplesand4,201tumorsamplesof15differentcancertypes.DNAmethylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selectiontoidentifycandidatemarkerswithhighmethylationacrossallcolorectaltumorswhileharboringlowmethylation i