Screening for Microsatellite Instability Identifies Frequent 3′-Untranslated Region Mutation of the RB1-Inducible Coiled-Coil 1 Gene in Colon Tumors 英文参考文献.docVIP

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Screening for Microsatellite Instability Identifies Frequent 3′-Untranslated Region Mutation of the RB1-Inducible Coiled-Coil 1 Gene in Colon Tumors 英文参考文献.doc

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Screening for Microsatellite Instability Identifies Frequent 3′-Untranslated Region Mutation of the RB1-Inducible Coiled-Coil 1 Gene in Colon Tumors 英文参考文献

ScreeningforMicrosatelliteInstabilityIdentifies Frequent39-UntranslatedRegionMutationoftheRB1- InducibleCoiled-Coil1GeneinColonTumors BogdanC.Paun1,YulanCheng1,BarbaraA.Leggett3,JoanneYoung4,StephenJ.Meltzer1,2 ,Yuriko Mori1* 1Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2Division of Gastroenterology,DepartmentofOncology,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica, 3ConjointGastroenterology Lab,RoyalBrisbaneHospitalFoundation,ClinicalResearchCentre,BancroftCentre,Herston,Queensland,Australia,4FamilialCancerLaboratory,QueenslandInstituteof MedicalResearch,Herston,Queensland,Australia Abstract Background:Codingregionmicrosatelliteinstability(MSI)resultsinlossofgeneproductsandpromotionofmicrosatellite- unstable(MSI-H)carcinogenesis.RecentstudieshaveindicatedthatMSIwithin39-untranslatedregions(39UTRs)maypost- transcriptionallydysregulategeneproducts.Withinthiscontext,weconductedabroadmutationalsurveyof42short39UTR microsatellites(MSs)in45MSI-Hcolorectaltumorsandtheircorrespondingnormalcolonicmucosae. Methodology/Principal Findings: In order to estimate the overall susceptibility of MSs to MSI in MSI-H tumors, the observedMSIfrequencyofeachMSwascorrelatedwithitslength,interspeciessequenceconservationlevel,anddistance from some genetic elements (i.e., stop codon, polyA signal, and microRNA binding sites). All MSs were stable in normal colonic mucosae. The MSI frequency at each MS in MSI-H tumors was independent of sequence conservation level and distancefromothergeneticelements.Incontrast,MSlengthcorrelatedsignificantlywithMSIfrequencyinMSI-Htumors (r=0.86, p=7.2610213). 39UTR MSs demonstrated MSI frequencies in MSI-H tumors higher than the 99% upper limit predicted by MS length for RB1-inducible coiled-coil 1(RB1CC1, mutation frequency 68.4%), NUAK family SNF1-like kinase 1(NUAK1,31.0%),andRtf1,Paf1/RNApolymeraseIIcomplexcomp