Nature：SNP被用于识别急性淋巴细胞性白血病的基因病灶

来源生物谷2007-4-1820:49:08Nature：SNP被用于识别急性淋巴细胞性白血病的基因病灶生物谷

生物谷报道：根据最新一期的《Nature》杂志的报道，利用SNP微阵列在整个基因组范围内对DNA版本数异常进行高分辨率分析的方法，被用来识别与儿童最常见的癌症―急性淋巴细胞性白血病有关的基因病灶。对来自242位患者的白血病母细胞所做的分析显示，在40%的B-先祖细胞急性淋巴细胞性白血病病例中，为B-淋巴细胞发育的关键调控因子编码的基因发生删除、放大、点突变和结构重排等问题。PAX5是最常见的目标。所获得的数据表明，能够绕开这些基因病灶所造成障碍的小分子细胞分化诱导因子可以作为研究新的治疗方法的一个重点，并且更具有普遍意义的是，它们展示了人们所熟悉的整个基因组范围内进行分析的方法作为识别癌症中新的小分子病灶的一种手段所具有的潜力。FIGURE1.EBF1deletionsinB-progenitorALL.a,EBF1exonsareindicatedbyverticallines.TheextentofEBF1deletionineachcaseisshownbyahorizontalline,withlargedeletionsdenotedbyarrowedlines.AsteriskindicatescaseBCRCABL-SNP#5examinedbyFISHasshowninc.b,Copynumber'heatmap'showingEBF1deletionineightB-progenitorALLcases.H,hypodiploid;O,other;Ph,BCRCABL1positive.c,EBF1FISHanalysisofcaseBCRCABL-SNP#5identifiestwodistinctblastpopulations,witheithermono-allelicorbi-allelicEBF1deletion;theEBF1probeisredandthecontrolprobeisgreen.d,TwodistinctblastpopulationsdifferinsurfaceexpressionofCD22andCD10.e,CorrelationofblastCD79AandCD10expression.f,FISHanalysisofcellssortedbyCD10expression.原文出处：NatureVolume446Number7137Genome-wideanalysisofgeneticalterationsinacutelymphoblasticleukaemiap758CharlesG.Mullighan,SalilGoorha,InaRadtke,ChristopherB.Miller,ElaineCoustan-Smith,JamesD.Dalton,KevinGirtman,SusanMathew,JingMa,StanleyB.Pounds,XiaopingSu,Ching-HonPui,MaryV.Relling,WilliamE.Evans,SheilaA.Shurtleff&JamesR.Downingdoi:10.1038/nature05690Abstract|FullText|PDF（941K）|SupplementaryinformationSeealso:Editor'ssummary|NewsandViewsbyGolub相关基因：PAX5OfficialSymbol:PAX5andName:pairedboxgene5（B-celllineagespecificactivator）[Homosapiens]OtherAliases:BSAPOtherDesignations:pairedbox5;pairedboxgene5（B-celllineagespecificactivatorprotein）;pairedboxhomeoticgene5;transcriptionfactorPAX5Chromosome:9;Location:9p13MIM:167414GeneID:5079作者简介：JamesR.Downing,MDMember,St.JudeFacultyScientificDirector,St.JudeChildren'sResearchHospitalChair,PathologyAssociateDirectorofBasicResearch,CancerCenterCo-Leader,HematologicalMalignanciesProgramDirector,MolecularPathologyLaboratoryDepartmentsPathologyContactInformationJamesR.Downing,MDScientificDirectorChairman,DepartmentofPathologyMS342,RoomD4047DSt.JudeChildren'sResearchHospital332N.LauderdaleMemphis,TN38105-2794USAE-mail:james.downing@stjude.orgPhone:（901）495-3510FAX:（901）495-3749EducationMD-UniversityofMichigan,AnnArbor（1981）ResearchInterestsDevelopmentalhematopoiesisandtheroleofAML1intheformationofhematopoieticstemcellsMechanismsofLeukemogenesisMousegeneticsClinicalapplicationsofexpressionprofilingSelectedPublicationsKagerL,CheokM,WenjianY,ZazaG,ChengQ,PanettaJC,PuiC-H,DowningJR,RellingM,EvansW.FolatePathwayGeneExpressionDiffersinSubtypesofAcuteLymphoblasticLeukemiaandInfluencesMethotrexatePharmacodynamics.JCI（inpress）2004.RossME,MahfouzR,OnciuM,LiuH-C,ZhouX,SongG,ShurtleffSA,PoundsS,ChengC,MaJ,RibeiroRC,RubnitzJE,GirtmanK,WilliamsWK,RaimondiSC,LiangD-C,ShihL-Y,PuiC-H,DowningJR.GeneExpressionProfilingofPediatricAcuteMyelogenousLeukemia.Blood104:3679-87,2004.PuiCH,SandlundJT,PeiD,CampanaD,RiveraGK,RibeiroRC,RubnitzJE,RazzoukBI,HowardSC,HudsonMM,ChengC,KunLE,RaimondiSC,BehmFG,DowningJR,RellingMV,EvansWE.Improvedoutcomeforchildrenwithacutelymphoblasticleukemia:resultsofTotalTherapyStudyXIIIBatSt.JudeChildren’sResearchHospital.Blood104:2690-2696,2004.SunWandDowningJR.HaploinsufficiencyofAML1resultsinadecreaseinthenumberofLTR-HSCs,whilesimultaneouslyinducinganincreaseinmorematureprogenitors.Blood104:3565-72,2004.ZazaG,YangW,KagerL,CheokM,DowningJR,PuiC-H,RellingMV,EvansWE.AcuteLymphoblasticleukemiawithTEL-AML1fusionhassignificantlylowerexpressionofgenesinvolvedinpurinemetabolismandcorrespondinglylowerdenovopurinesynthesis.Blood104:1435-41,2004.ImaiC,RossME,ReidG,Coustan-SmithE,SchultzKR,PuiCH,DowningJR,CampanaD.ExpressionoftheadaptorproteinBLINK/SLP-65inchildhoodacutelymphoblasticleukemia.Leukemia18:922-5,2004.PuiCH,RellingMV,SandlundJT,DowningJR,CampanaD,EvansWE.RationaleandDesignofTotalTherapyStudyXVforNewlyDiagnosedChildhoodAcuteLymphoblasticLeukemia.AnnHematol83（suppl1）:S124-126,2004.LorsbachRB,MooreJ,AngSO,SunW,LennyN,DowningJR.RoleofRUNX1inadulthematopoiesis:analysisofRUNX1-IRES-GFPknock-inmicerevealsdifferentiallineageexpression.Blood103:2522-9,2004.FeldmanAL,MinnitiC,SantiMariarita,DowningJR,RaffeldM,JaffeES.Histiocyticsarcomafollowingacutelymphoblasticleukaemia:evidenceforacommonclonalorigin.TheLancetOncology5:248-250,2004.PuiCH,SandlundJT,PeiD,RiveraGK,HowardSC,RibeiroRC,RubnitzJE,RazzoukBI,HudsonMM,ChengC,RaimondiSC,BehmFG,DowningJR,RellingMV,EvansWE.Resultsoftherapyforacutelymphoblasticleukemiainblackandwhitechildren.JAMA290:2001-7,2003.Coustan-SmithE,RibeiroRC,RubnitzJE,RazzoukBI,PuiCH,PoundsS,AndreanskyM,BehmFG,RaimondiSC,ShurtleffSA,DowningJR,CampanaD.Clinicalsignificanceofresidualdiseaseduringtreatmentinchildhoodacutemyeloidleukemia.BritishJournalofHaematology123:243-52,2003.OnciuM,BehmFG,DowningJR,ShurtleffSA,RaimondiSC,MaZ,MorrisSW,KennedyW,JonesSC,SandlundJT.ALK-positiveplasmablasticB-celllymphomawithexpressionoftheNPM-ALKfusiontranscript:reportof2cases.Blood102:2642-4,2003.RossME,XiaodongZ,SongG,ShurtleffSA,GirtmanK,WilliamsWK,LiuHC,MahfouzR,RaimondiSC,LennyN,PatelA,DowningJR.ClassificationofPediatricAcuteLymphoblasticLeukemiabyGeneExpressionProfiling.Blood102:2951-9,2003.CheokMH,YangW,PuiCH,DowningJR,ChengC,NaeveCW,RellingMV,EvansWE.Treatment-specificchangesingeneexpressiondiscriminateinvivodrugresponseinhumanleukemiacells.NatureGenetics34:85-90,2003.LorsbachR,MooreJ,MathewS,RaimondiSC,MukatiraST,DowningJR.TET1,amemberofanovelproteinfamily,isfusedtoMLLinacutemyeloidleukemiacontainingthet（10;11）（q22;q23）.Leukemia17:637-41,2003.LiJ,LiuH,DowningJR,YeohAE,WongL.Simplerulesunderlyinggeneexpressionprofilesofmorethansixsubtypesofacutelymphoblasticleukemia（ALL）patients.Bioinformatics19:71-78,2003.TonksA,PearnL,TonksAJ,PearceL,HoyT,PhillipsS,FisherJ,DowningJR,BurnettAK,DarleyRL.AML1-ETOpromotesextensiveself-renewalofhumanprimaryerythroidcells.Blood101:624-32,2003.HillDA,RiedleySE,PatelAR,ShurtleffSA,HyerJ,CainAM,BillupsCA,DowningJR,PappoAS.Real-timePolymeraseChainReactionasanAidfortheDetectionofSYT-SSX1andSYT-SSX2TranscriptsinFreshandArchivalPediatricSynovialSarcomaSpecimens:Reportof25CasesfromSt.JudeChildren’sResearchHospital.PediatrDevPathol6:24-34,2003.RubnitzJE,RaimondiSC,HalbertAR,TongX,SrivastavaKD,RazzoukBI,PuiCH,DowningJR,RibeiroRC,BehmFG.Characteristicsandoutcomeoft（8;21）-positivechildhoodacutemyeloidleukemia:asingleinstitution’sexperience.Leukemia16:2072-7,2002.KoganSC,AnverJB,BraytonC,CardiffRD,CarterJ,CoronadoSD,DowningJR,FredicksonT,HainesDC,HarrisA,HarrisNL,HiaiH,JaffeES,MacLennanI,MufsonRA,PandolfiPP,PattengaleP,PerkinsAS,SimpsonRM,TuttleM,WardJM,WongJ,MorseIIIHC.Bethesdaproposalsfortheclassificationofnonlymphoidhematopoieticneoplasmsinmice.Blood100:238-45,2002.DowningJR,ShannonKM.Acuteleukemia:Apediatricperspective.CancerCell2:437-445,2002.YeohE,RossME,ShurtleffSA,WilliamsWK,PatelD,MahfouzR,BehmFG,RaimondiSC,RellingMV,PatelA,ChengC,CampanaD,WilkinsD,ZhouX,JinyanL,LiuH,PuiCH,EvansWE,NaeveC,WongL,DowningJR.Classification,subtypediscovery,andpredictionofoutcomeinpediatricacutelymphoblasticleukemiabygeneexpressionprofiling.CancerCell1:133-143,2002.FerrandoAA,NeubergDS,StauntonJ,LohML,HuardC,RaimondiSC,BehmFG,PuiC-H,DowningJR,GillilandDG,LanderES,GolubTR,LookAT.GeneExpressionSignaturesDefineNovelOncogenicPathwaysisT-CellAcuteLymphoblasticLeukemia.CancerCell1:75-87,2002.HiguchiH,O’BrienD,DowningJR.ExpressionofaconditionalAML1-ETOoncogenebypassesembryoniclethalityandestablishesamurinemodelofhumant（8;21）acutemyeloidleukemia.CancerCell1:63-74,2002.AmannJM,NipJ,StromDK,LutterbachB,HaradaH,Lenny,N,DowningJR,MeyersS,HiebertSW.ETO,atargetoft（8;21）inacuteleukemia,makesdistinctcontactswithmultiplehistonedeacetylasesandbindsmSin3Athroughitsoligomerizationdomain.MolCellBiology21:6470-83,2001.DangJ,InukaiT,KurosawaH,GoiK,InabaT,LennyNT,DowningJR,StifaniS,LookAT.TheE2A-HLFoncoproteinactivatesGroucho-relatedgenesandsuppressesRunx1.MolCellBiology21:5935-45,2001.HaradaY,HaradaH,DowningJR,KimuraA.Ahematopoietic-specifictransmembraneprotein,Art-1,ispossiblyregulatedbyAML1.BiochemBiophyResComm284:714-722,2001.DowningJR.AML1/CBFâtranscriptioncomplex;itsroleinnormalhematopoiesisandleukemia.Leukemia15:664-665,2001.MathewS,RaoPH,DaltonJ,DowningJR,RaimondiSC.Multicolorspectralkaryotypingidentifiesnoveltranslocationsinchildhoodacutelymphoblasticleukemia.Leukemia15:664-665,2001.ShihL-Y,FuJ-F,ShurtleffSA,MorrisSW,DowningJR.LackofBCL10mutationsinmultiplemyelomaandplasmacellleukemia.GenesChromCancer30:402-406,2001.AthaleUH,ShurtleffS,JenkinsJJ,PoquetteCA,TanM,DowningJR,PappoAS.Useofrhabdomyosarcoma,Ewing’ssarcomafamilyoftumors,anddesmoplasticsmallroundcelltumor.JPediatrHematolOncol23:99-104,2001.BonillaM,MorenoN,MarinaN,deReyesG,ShurtleffSA,DowningJR,BehmFG,HarrisonPL,RibeiroRC,PenaO,CristWM,AntillonFG.Acutelymphoblasticleukemiainadevelopingcountry:preliminaryresultsofanonrandomizedclinicaltrialinElSalvador.JPediatrHematolOncol22:495-501,2000.DowningJR,HiguchiM,LennyN,YeohAE.AlterationsoftheAML1transcriptionfactorinhumanleukemia.SeminCellDevBiol11:347-360,2000.CaiZ,deBruijnM,MaX,DortlandB,LuteijnT,DowningJR,DzierzakE.HaploinsuffiencyofAML1affectsthetemporarlandspatialgenerationofhematopoieticstemcellsinthemouseembryo.Immunity12:423-431,2000.StromDK,NipJ,WestendorfJJ,LinggiB,LutterbachB,DowningJR,LennyN,HiebertSW.ExpressionoftheAML1oncogeneshortenstheG1phaseofthecellcycle.JBiolChem275:3438-3445,2000.OkudaT,TakedaK,FujitaY,NishimuraM,YagyuS,YoshidaM,AkiraS,DowningJR,AbeT.Biologicalcharacteristicsoftheleukemia-associatedtranscriptionalfactorAML1disclosehematopoieticrescueofAML-deficientembryonicstemcellsbyusingaknock-instrategy.MolCellBiol20:319-328,2000.RubnitzJE,DowningJR,PuiCH.SignificanceoftheTEL-AMLfusiongeneinchildhoodAML.Leukemia13:1470-1471,1999GolubTR,SlonimDK,TamayoP,HuardC,GaasenbeekM,MesirovJP,CollerH,LohML,DowningJR,CaligiuriMA,BloomfieldCD,LanderES.Molecularclassificationofcancer:classdiscoveryandclasspredictionbygeneexpressionmonitoring.Science286（5439）:531-537,1999.HaradaH,HaradaY,O'BrienDP,RiceDS,NaeveCW,DowningJR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