Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes 英文参考文献.docVIP

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Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes 英文参考文献.doc

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Mouse p53-Deficient Cancer Models as Platforms for Obtaining Genomic Predictors of Human Cancer Clinical Outcomes 英文参考文献

Mousep53-DeficientCancerModelsasPlatformsfor ObtainingGenomicPredictorsofHumanCancerClinical Outcomes MartaDuen?as1,MirentxuSantos1,JuanF.Aranda1,ConchaBielza2,AnaB.Mart?′nez-Cruz1,CorinaLorz1, MiquelTaron3,EvaM.Ciruelos4,Jose′ L.Rodr?′guez-Peralto5,MiguelMart?′n6,PedroLarran?aga2, JubrailDahabreh7,GeorgeP.Stathopoulos8,RafaelRosell3,Jesu′sM.Paramio1*,Ramo′nGarc?′a- Escudero1* 1Molecular Oncology Unit, CIEMAT, Madrid, Spain, 2Departamento de Inteligencia Artificial, Universidad Polite′cnica de Madrid, Boadilla del Monte, Madrid, Spain, 3CatalanInstituteofOncology,HospitalGermansTriasiPujol,Badalona,Spain,4MedicalOncologyDepartment,HospitalUniversitario12deOctubre,Madrid,Spain, 5Pathology Department, Hospital Universitario 12 de Octubre, and Instituto de Investigacio′n Hospital 12 de Octubre i+12, Universidad Complutense, Madrid, Spain, 6HospitalGeneralGregorioMaran?o′n,UniversidadComplutense,Madrid,Spain,7SurgeryDepartment,AthensMedicalCenter,Athens,Greece,8OncologyDepartment, ErrikosDunantHospital,Athens,Greece Abstract MutationsintheTP53geneareverycommoninhumancancers,andareassociatedwithpoorclinicaloutcome.Transgenic mousemodelslackingtheTrp53geneorthatexpressmutantTrp53transgenesproducetumourswithmalignantfeatures inmanyorgans.Wepreviouslyshowedthetranscriptomeofap53-deficientmouseskincarcinomamodeltobesimilarto thoseofhumancancerswithTP53mutationsandassociatedwithpoorclinicaloutcomes.Thisreportshowsthatmuchof the682-genesignatureofthismurineskincarcinomatranscriptomeisalsopresentinbreastandlungcancermousemodels inwhichp53isinhibited.Further,wereportvalidatedgene-expression-basedtestsforpredictingtheclinicaloutcomeof humanbreastandlungadenocarcinoma.Itwasfoundthathumanpatientswithcancercouldbestratifiedbasedonthe similarityoftheirtranscriptomewiththemouseskincarcinoma682-genesignature.Theresultsalsoprovidenewtargetsfor thetreatmentofp53-defectivetumours. Citation: Duen?as M, Santos M, Aranda JF, Bielza C, Mart?′nez-Cruz AB, et al. (2012) Mouse p53-Deficient C