NOTCH2 Is Neither Rearranged nor Mutated in t(1;19) Positive Oligodendrogliomas 英文参考文献.docVIP
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NOTCH2 Is Neither Rearranged nor Mutated in t(1;19) Positive Oligodendrogliomas 英文参考文献
NOTCH2IsNeitherRearrangednorMutatedint(1;19)
PositiveOligodendrogliomas
MagdalenaBenetkiewicz1,2,AhmedIdbaih3,4,5,Pierre-YvesCousin1,2,BlandineBoisselier3,4 ,Yannick
Marie3,4,EmmanuelleCrinie`re3,4,Khe? Hoang-Xuan3,4,5,Jean-YvesDelattre3,4,5,MarcSanson3,4,5 ,Olivier
Delattre1,2
*
1INSERM,Unite′ 830,Paris,France,2InstitutCurie,SectionRecherche,Unite′ deGe′ne′tique etBiologiedesCancers,Paris,France,3INSERM,Unite′ 711,Groupehospitalier
Pitie′-Salpe?trie`re, Paris, France, 4Universite′ Pierre et Marie Curie-Paris 6, Laboratoire Biologie des Interactions Neurone-Glie, Groupe hospitalier Pitie′-Salpe?trie`re, Paris,
France,5AP-HP,GroupehospitalierPitie′-Salpe?trie`re, ServicedeneurologieMazarin,Paris,France
Abstract
Thecombineddeletionof1pand19qchromosomal arms isfrequentinoligodendrogliomas(OD)andhasrecentlybeen
shownto be mediated by an unbalanced t(1;19) translocation. Recentstudies of 1p/19qco-deletedOD suggest thatthe
NOTCH2geneisimplicatedinoligodendrocytedifferentiationandmaybeinvolvedinthisrearrangement.Theobjectiveofthe
presentstudywastoanalyzetheNOTCH2locuseitherasachromosomaltranslocationlocusthatmaybealteredbythe1p/19q
recurrentrearrangementorasagenethatmaybeinactivatedbyatwohitprocess.Weperformedanarray-CGHanalysisof15
ODspresenting1p/19qco-deletionusingahigh-densityoligonucleotidemicroarrayspanning1pand19qpericentromeric
regionswith377bpaverageprobespacing.Weshowedthatthe1pdeletionextendstothecentromereofchromosome1and
includestheentireNOTCH2gene.Nointernalrearrangementofthisgenewasobserved.Thisstronglysuggeststhatthet(1;19)
translocation does not lead to an abnormal NOTCH2 structure. The analysis of the entire NOTCH2 coding sequence was
performed in four cases and did not reveal any mutation therefore indicating that NOTCH2 does not harbor genetic
characteristicsofatumorsuppressorgene.Finally,thedetailedanalysisofchromosome19pericentromericregionledtothe
identificationoftwobreakpointclustersat19p12and19q11–12.Interestingly, thesetworeg
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