Amplified and Homozygously Deleted Genes in Glioblastoma Impact on Gene Expression Levels 英文参考文献.docVIP
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Amplified and Homozygously Deleted Genes in Glioblastoma Impact on Gene Expression Levels 英文参考文献
AmplifiedandHomozygouslyDeletedGenesin
Glioblastoma:ImpactonGeneExpressionLevels
Ine?sCrespo1,2,Herm?′nioTa?o3,AnaBelenNieto4,OlindaRebelo5,Patr?′ciaDomingues1,2 ,Ana
Lu?′saVital1,2,MariadelCarmenPatino6,MarcosBarbosa3,7,MariaCelesteLopes1,2 ,Catarina
ResendeOliveira1,7,AlbertoOrfao4,9,Mar?′aDoloresTabernero4,8,9
*
1CentreforNeuroscienceandCellBiology,UniversityofCoimbra,Coimbra,Portugal,2FacultyofPharmacy,UniversityofCoimbra,Coimbra,Portugal,3Neurosurgery
Service, University Hospital of Coimbra, Coimbra, Portugal, 4Centre for Cancer Research (CIC IBMCC-CSIC/USAL), Department of Medicine, University of Salamanca,
Salamanca, Spain, 5Neuropathology Laboratory, Neurology Service, University Hospital of Coimbra, Coimbra, Portugal, 6Department of Statistics, University of
Salamanca,Salamanca,Spain,7FacultyofMedicine,UniversityofCoimbra,Coimbra,Portugal,8InstitutodeEstudiosdeCienciasdelaSaluddeCastillayLeo′n(IECSCYL),
Soria,Spain,9InstitutoBiosanitariodeSalamanca(IBSAL)-ResearchUnitoftheUniversityHospitalofSalamanca,Salamanca,Spain
Abstract
Background:Glioblastomamultiforme(GBM)displaysmultipleampliconsandhomozygousdeletionsthatinvolverelevant
pathogenicgenesandothergeneswhoseroleremainsunknown.
Methodology:Single-nucleotidepolymorphism(SNP)-arrayswereusedtodeterminethefrequencyofrecurrentamplicons
andhomozygousdeletionsinGBM(n=46),andtoevaluatetheimpactofcopynumberalterations(CNA)onmRNAlevelsof
thegenesinvolved.
PrincipalFindings:Recurrentampliconsweredetectedforchromosomes7(50%),12(22%),1(11%),4(9%),11(4%),and17
(4%),whereashomozygousdeletionsinvolvedchromosomes9p21(52%)and10q(22%).Mostgenesthatdisplayedahigh
correlationbetweenDNACNAandmRNAlevelswerecodedintheamplifiedchromosomes.Forsomeampliconstheimpact
ofDNACNAonmRNAexpressionwasrestrictedtoasinglegene(e.g.,EGFRat7p11.2),whileforothersitinvolvedmultiple
genes (e.g., 11 and 5 genes at 12q14.1–q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31)
includedmultiplegenes,associationbetweentheseDNAC
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