Somatic LKB1 Mutations Promote Cervical Cancer Progression 英文参考文献.docVIP

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Somatic LKB1 Mutations Promote Cervical Cancer Progression 英文参考文献.doc

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Somatic LKB1 Mutations Promote Cervical Cancer Progression 英文参考文献

SomaticLKB1MutationsPromoteCervicalCancer Progression ShanaN.Wingo1,TeresaD.Gallardo2,EsraA.Akbay2,Mei-ChiLiang3,CristinaM.Contreras2 ,Todd Boren1,TakeshiShimamura3,DavidS.Miller1,NormanE.Sharpless4,NabeelBardeesy5,DavidJ. Kwiatkowski6,JohnO.Schorge7,Kwok-KinWong3,DiegoH.Castrillon2* 1DivisionofGynecologicOncology,UTSouthwesternMedicalCenter,Dallas,Texas,UnitedStatesofAmerica,2DepartmentofPathology,UTSouthwesternandSimmons ComprehensiveCancerCenter,Dallas,Texas,UnitedStatesofAmerica,3DepartmentofMedicalOncology,DanaFarberCancerInstitute,Boston,Massachusetts,United StatesofAmerica,4DepartmentsofMedicineandGenetics,LinebergerComprehensiveCancerCenter,UniversityofNorthCarolinaSchoolofMedicine,ChapelHill,North Carolina,UnitedStatesofAmerica,5MassachusettsGeneralHospitalCancerCenter,Boston,Massachusetts,UnitedStatesofAmerica,6DepartmentofMedicine,Brigham andWomen’sHospital,Boston, Massachusetts,UnitedStatesofAmerica,7DivisionofGynecologicOncology,MassachusettsGeneralHospital,Boston,Massachusetts, UnitedStatesofAmerica Abstract HumanPapilloma Virus(HPV) is the etiologic agent for cervical cancer. Yet, infection withHPV is not sufficient tocause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrentgeneticalterationshavebeenidentifiedincervicalcancers.Thus,thepressingquestionastothebiologicalbasis of cervical cancer progression has remained unresolved, hampering thedevelopment of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor.Approximatelyone-halfoftumorswithmutationsharboredsinglenucleotidesubstitutionsormicrodeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplexligationprobeamplification(MLPA).Bia