Copynumbervariationsareprogressivelyassociatedwiththepathogenesisofcolorectalcancerinulcerativecolitis

摘要： AIM:Toevaluatetheassociationofknowncopynumbervariations(CNVs)inulcerativecolitis(UC)progressingtocolorectalcancer.METHODS:MicrosatelliteinstabilityanalysisusingtheNationalCancerInstitutespanelofmarkers,andCNVassociationstudiesusingAgilent2×105karraysweredoneintissuesamplesfromfourpatientgroupswithUC:thoseatlowrisk(LR)orhighriskofdevelopingcolorectalcancer,thosewithpremalignantdysplasticlesions,andthosewithcolitis-associatedcolorectalcancer(CAC).DNAfromtissuesamplesofthesegroupswereindependentlyhybridizedonarraysandanalyzed.ThedataobtainedwerefurthersubjectedtodownstreambioinformaticsenrichmentanalysistoexaminethecorrelationwithCACprogression.RESULTS:MicroarrayanalysishighlightedaprogressiveincreaseinthetotalnumberofCNVs[LR(n=178)vsCAC(n=958),5.3-fold],gainsandlosses[LR(n=37and141)vsCAC(n=495and463),13.4-and3.3-fold,respectively],size[LR(964.2kb)vsCAC(10540kb),10.9-fold]andthenumberofgenesinsuchregions[LR(n=119)vsCAC(n=455),3.8-fold].ChromosomewiseanalysisofCNVsalsoshowedanincreaseinthenumberofCNVsacrosseachchromosome.Therewere38genescommontoallfourgroupsinthestudy;13ofthesewerecommontocancergenesfromtheGeneticDiseaseAssociationdataset.Thegenesetenrichmentanalysisandontologyanalysishighlightedmanycancerassociatedgenes.Allthesamplesinthedifferentgroupsweremicrosatellitestable.CONCLUSION:IncreasingnumbersofCNVsareassociatedwiththeprogressionofUCtoCAC,andwarrantfurtherdetailedexploration. ... （共7页）