High Fragmentation Characterizes Tumour-Derived Circulating DNA 英文参考文献.docVIP

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High Fragmentation Characterizes Tumour-Derived Circulating DNA 英文参考文献.doc

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High Fragmentation Characterizes Tumour-Derived Circulating DNA 英文参考文献

HighFragmentationCharacterizesTumour-Derived CirculatingDNA FlorentMouliere1,BrunoRobert2,ErikaArnauPeyrotte1,MaguyDelRio2,MarcYchou3,FranckMolina1, CelineGongora2,AlainR.Thierry1* 1SysDiagUMR3145–CNRS,NationalCentreoftheScientificResearch/BIO-RAD,Montpellier,France,2U896INSERM,NationalInstituteofHealthandMedicalResearch, UniversityMontpellier1,IRCM,InstituteofOncologicalResearchofMontpellier,Montpellier,France,3CRLC,RegionalCentreagainstCancer,Vald’Aurelle-PaulLamarque, Montpellier,France Abstract Background: Circulating DNA (ctDNA) is acknowledged as a potential diagnostic tool for various cancers including colorectal cancer, especially when considering the detection of mutations. Certainly due to lack of normalization of the experimental conditions, previous reports present many discrepancies and contradictory data on the analysis of the concentrationoftotalctDNAandontheproportionoftumour-derivedctDNAfragments. Methodology:InordertorigorouslyanalysectDNA,wethoroughlyinvestigatedctDNAsizedistribution.Weusedahighly specificQ-PCRassayandathymicnudemicexenograftedwithSW620orHT29humancoloncancercells,andwecorrelated ourresultsbyexaminingplasmafrommetastaticCRCpatients. Conclusion/Significance:Fragmentationandconcentrationoftumour-derivedctDNAispositivelycorrelatedwithtumour weight.CtDNAquantificationbyQ-PCRdependsontheamplifiedtargetlengthandisoptimalfor60–100bpfragments.Q- PCRanalysisofplasmasamplesfromxenograftedmiceandcancerpatientsshowedthattumour-derivedctDNAexhibitsa specific amount profile based on ctDNA size and significant higher ctDNA fragmentation. Metastatic colorectal patients (n=12)showednearly5-foldhighermeanctDNAfragmentationthanhealthyindividuals(n=16). Citation:MouliereF,RobertB,ArnauPeyrotteE,DelRioM,YchouM,etal.(2011)HighFragmentationCharacterizesTumour-DerivedCirculatingDNA.PLoS ONE6(9):e23418.doi:10.1371/journal.pone.0023418 Editor:TerenceLee,UniversityofHongKong,HongKong ReceivedMay5,2011;AcceptedJuly16,2011;PublishedSeptember6,2011 Copyright: