Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia Related Splice Variant of LAMA3 Associated with a Poor Prognosis 英文参考文献.docVIP

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Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia Related Splice Variant of LAMA3 Associated with a Poor Prognosis 英文参考文献.doc

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Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia Related Splice Variant of LAMA3 Associated with a Poor Prognosis 英文参考文献

ExonArrayAnalysisofHeadandNeckCancersIdentifies aHypoxiaRelatedSpliceVariantofLAMA3Associated withaPoorPrognosis CarlaS.Moller-Levet1,2.*,GuyN.J.Betts2.,AdrianL.Harris3,JarrodJ.Homer4,CatharineM.L.West2, CrispinJ.Miller1 1AppliedComputationalBiologyandBioinformaticsGroup,CancerResearchUKPatersonInstituteforCancerResearch,TheUniversityofManchester,ChristieHospital, Manchester,UnitedKingdom,2TranslationalRadiobiologyGroup,SchoolofCancerandImagingSciences,TheUniversityofManchester,ChristieHospital,Manchester, UnitedKingdom,3CancerResearchUKMolecularOncologyLaboratories,WeatherallInstituteofMolecularMedicine,JohnRadcliffeHospital,Oxford,UnitedKingdom, 4DepartmentofOtolaryngology-HeadandNeckSurgery,TheUniversityofManchesterAcademicHealthScienceCentre,ManchesterRoyalInfirmary,Manchester,United Kingdom Abstract The identification of alternatively spliced transcript variants specific to particular biological processes in tumours should increaseourunderstandingofcancer.Hypoxiaisanimportantfactorincancerbiology,andassociatedsplicevariantsmay presentnewmarkerstohelpwithplanningtreatment.Amethodwasdevelopedtoanalysealternativesplicinginexonarray data,usingprobesetmultiplicitytoidentifygeneswithchangesinexpressionacrosstheirloci,andacombinationofthe splicingindexandanewmetricbasedonthevariationofreliabilityweightedfoldchangestodetectchangesinthesplicing patterns. The approach was validated on a cancer/normal sample dataset in which alternative splicing events had been confirmedusingRT-PCR.Wethenanalysedtenheadandnecksquamouscellcarcinomasusingexonarraysandidentified differentiallyexpressedsplicevariantsinfivesampleswithhighversusfivewithlowlevelsofhypoxia-associatedgenes.The analysis identified a splice variant of LAMA3 (Laminin a 3), LAMA3-A, known to be involved in tumour cell invasion and progression. The full-length transcript of the gene(LAMA3-B) did notappear tobe hypoxia-associated. The results were confirmedusingqualitativeRT-PCR.Inaseriesof59prospectivelycollectedhead