Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer 英文参考文献.docVIP

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Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer 英文参考文献.doc

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Analysis of Cancer Mutation Signatures in Blood by a Novel Ultra-Sensitive Assay Monitoring of Therapy or Recurrence in Non-Metastatic Breast Cancer 英文参考文献

AnalysisofCancerMutationSignaturesinBloodbya NovelUltra-SensitiveAssay:MonitoringofTherapyor RecurrenceinNon-MetastaticBreastCancer ZhenbinChen1,JinongFeng1,CarolynH.Buzin2,6,QiangLiu2,LawrenceWeiss3,KempKernstine4, GeorgeSomlo5,SteveS.Sommer1,2,6* 1DepartmentofMolecularGenetics,CityofHopeNationalMedicalCenter,Duarte,California,UnitedStatesofAmerica, 2DepartmentofMolecularDiagnosis,Cityof HopeNationalMedicalCenter,Duarte,California,UnitedStatesofAmerica,3DepartmentofAnatomicPathology,CityofHopeNationalMedicalCenter,Duarte,California, UnitedStatesofAmerica,4DivisionofSurgery,CityofHopeNationalMedicalCenter,Duarte,California,UnitedStatesofAmerica,5DepartmentofMedicalOncology,City ofHopeNationalMedicalCenter,Duarte,California,UnitedStatesofAmerica,6MEDomics,LLC,Azusa,California,UnitedStatesofAmerica Abstract Background:TumorDNAhasbeenshowntobepresentbothincirculatingtumorcellsinbloodandasfragmentsinthe plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimatemarkertomeasureefficacyofcancertherapyand/orearlyrecurrence.Hereinwepresentamethodfordetecting microinsertions/deletions/indels(MIDIs)atultra-highanalyticalselectivity.MIDIscompriseabout15%ofmutations. MethodsandFindings:WedescribeMIDI-ActivatedPyrophosphorolysis(MAP),amethodofultra-highanalyticalselectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplexslippageandmis-pyrophosphorolysis.MAPgenerallyhasananalyticalselectivityofonemutantmoleculeper .1billionwildtypemoleculesandananalyticalsensitivityofonemutantmoleculeperreaction.Theanalyticalselectivityof MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allelespecificamplification(PAP-A)fordetectingMIDIs.Theutilityofthismethodisillustratedintwoways. 1)WedemonstratethattwoEGFRdeletionscommonlyfoundinlungcancersarenotpresentintissuef