Analysis of Multiple Sarcoma Expression Datasets Implications for Classification, Oncogenic Pathway Activation and Chemotherapy Resistance 英文参考文献.docVIP
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Analysis of Multiple Sarcoma Expression Datasets Implications for Classification, Oncogenic Pathway Activation and Chemotherapy Resistance 英文参考文献
AnalysisofMultipleSarcomaExpressionDatasets:
ImplicationsforClassification,OncogenicPathway
ActivationandChemotherapyResistance
PanagiotisA.Konstantinopoulos1.,ElenaFountzilas1.,JeffreyD.Goldsmith2,ManojBhasin3 ,Kamana
Pillay1,NancyFrancoeur1,TowiaA.Libermann3,MarkC.Gebhardt4,DimitriosSpentzos1,3*
1DivisionofHematology/Oncology,DepartmentofMedicine,BethIsraelDeaconessMedicalCenterandHarvardMedicalSchool,Boston,Massachusetts,UnitedStatesof
America,2DepartmentofPathology,BethIsraelDeaconessMedicalCenterandHarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,3Genomics
CenterandDivisionofInterdisciplinaryMedicineandBiotechnology,DepartmentofMedicine,BethIsraelDeaconessMedicalCenterandHarvardMedicalSchool,Boston,
Massachusetts,UnitedStatesofAmerica,4DepartmentofOrthopedicSurgery,BethIsraelDeaconessMedicalCenterandHarvardMedicalSchool,Boston,Massachusetts,
UnitedStatesofAmerica
Abstract
Background:Diagnosisofsofttissuesarcomas(STS)ischallenging.Manyremainunclassified(not-otherwise-specified,NOS)
orgroupedincontroversialcategoriessuchasmalignantfibroushistiocytoma(MFH),withuncleartherapeuticvalue.We
analyzed several independent microarray datasets, to identify a predictor, use it to classify unclassifiable sarcomas, and
assessoncogenicpathwayactivationandchemotherapyresponse.
Methodology/PrincipalFindings:Weanalyzed5independentdatasets(325tumorarrays).Wedevelopedandvalidateda
predictor,whichwasusedtoreclassifyMFHandNOSsarcomas.Themolecular‘‘match’’betweenMFHandtheirpredicted
subtypes was assessed using genome-wide hierarchical clustering and Subclass-Mapping. Findings were validated in 15
paraffin samples profiled on the DASL platform. Bayesian models of oncogenic pathway activation and chemotherapy
responsewereappliedtoindividualSTSsamples.A170-genepredictorwasdevelopedandindependentlyvalidated(80-85%
accuracyinalldatasets).MostMFHandNOStumorswerereclassifiedasleiomyosarcomas,liposarcomasandfibrosarcomas.
‘‘Molecular match’’ between MFH and their predicted ST
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