Selection of Microsatellite Markers for Bladder Cancer Diagnosis without the Need for Corresponding Blood 英文参考文献.docVIP

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Selection of Microsatellite Markers for Bladder Cancer Diagnosis without the Need for Corresponding Blood 英文参考文献.doc

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Selection of Microsatellite Markers for Bladder Cancer Diagnosis without the Need for Corresponding Blood 英文参考文献

SelectionofMicrosatelliteMarkersforBladderCancer DiagnosiswithouttheNeedforCorrespondingBlood AngelaA.G.vanTilborg1,LucieC.Kompier1,IreneLurkin1,RicardoPoort1,SamiraElBouazzaoui1, KirstinvanderKeur1,TahlitaZuiverloon1,LarsDyrskjot2,TorbenF.Orntoft2,MoniqueJ.Roobol3, EllenC.Zwarthoff1* 1DepartmentofPathology,ErasmusMC,Rotterdam,TheNetherlands,2AarhusUniversityHospital,DepartmentofClinicalBiochemistry,Skejby,Denmark,3Department ofUrology,ErasmusMC,Rotterdam,TheNetherlands Abstract Microsatellitemarkersareusedforloss-of-heterozygosity,allelicimbalanceandclonalityanalysesincancers.Usually,tumor DNAiscomparedtocorrespondingnormalDNA.However,normalDNAisnotalwaysavailableandcandisplayaberrant alleleratiosduetocopynumbervariationsinthegenome.Moreover,stutterpeaksmaycomplicatetheanalysis.Touse microsatellitemarkersfordiagnosisofrecurrentbladdercancer,weaimedtoselectmarkerswithoutstutterpeaksanda constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markerswithtri-andtetranucleotiderepeatsinregionscommonlylostinbladdercancer.Basedonanalysisof50blood DNAsthe12bestperformingmarkerswereselectedwithfewstutterpeaksandaconstantratiobetweenpeaksheights.Per markerupperandlowercutoffvaluesforalleleratiosweredetermined.LOHofthemarkerswasobservedin59/104tumor DNAs.Wethendeterminedthesensitivityofthemarkerpanelfordetectionofrecurrentbladdercancerbyassaying102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstratethatup-frontselectionofmicrosatellitemarkersobliteratestheneedforacorrespondingbloodsample.For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospectiveanalysisofarchivaltumorsamplesforallelicimbalance. Citation:vanTilborgAAG,KompierLC,LurkinI,PoortR,ElBouazzaouiS,etal.(2012)SelectionofMicrosatelliteMarkersforBladderCancerDiagnosiswithoutthe NeedforCorrespondingBlood