《Mutational Landscape of Pediatric AcuteLymphoblastic Leukemia兒童急性突變景觀 淋巴母細胞性白血病》由會員上傳分享，免費在線閱讀，更多相關內(nèi)容在學術論文-天天文庫。

1、PublishedOnlineFirstNovember21,2016;DOI:10.1158/0008-5472.CAN-16-1303CancerMolecularandCellularPathobiologyResearchMutationalLandscapeofPediatricAcuteLymphoblasticLeukemia1111Ling-WenDing,Qiao-YangSun,Kar-TongTan,WenwenChien,112,3AnandMayakondaThippeswamy,AllenEngJuhYeoh,No

2、rihikoKawamata,4111,31,5YasunobuNagata,Jin-FenXiao,Xin-YiLoh,De-ChenLin,ManojGarg,111114,6Yan-YiJiang,LiangXu,Su-LinLim,Li-ZhenLiu,VikasMadan,MasashiSanada,1137LuciaTorresFernandez,HemaPreethi,MichaelLill,HagopM.Kantarjian,78,9104StevenM.Kornblau,SatoruMiyano,Der-CherngLia

3、ng,SeishiOgawa,1111,2Lee-YungShih,HenryYang,andH.PhillipKoef?erAbstractCurrentstandardofcareforpatientswithpediatricacutelym-recurrentmutationalhotspotswereobservedinepigeneticregula-phoblasticleukemia(ALL)ismainlyeffective,withhighremissiontorsCREBBP(R1446C/H),WHSC1(E1099K

4、),andthetyrosineratesaftertreatment.However,thegeneticperturbationsthatgivekinaseFLT3(K663R,N676K).ThemutantWHSC1wasestablishedrisetothisdiseaseremainlargelyunde?ned,limitingtheabilitytoasagain-of-functiononcogene,whiletheepigeneticregulatoraddressresistanttumorsordevelople

5、sstoxictargetedtherapies.ARID1AandtranscriptionfactorCTCFwerefunctionallyidenti?edHere,wereporttheuseofnext-generationsequencingtointerro-aspotentialtumorsuppressors.Analysisof28diagnosis/relapsegatethegeneticandpathogenicmechanismsof240pediatricALLtriopatientsplus10relapse

6、casesrevealedfourevolutionarycaseswiththeirmatchedremissionsamples.Commonlymutatedpathsanduncoveredtheorderingofacquisitionofmutationsingenesfellintoseveralcategories,includingRAS/receptortyrosinethesepatients.Thisstudyprovidesadetailedmutationalportraitkinases,epigeneticre

7、gulators,transcriptionfactorsinvolvedinofpediatricALLandgivesinsightsintothemolecularpathogen-lineagecommitment,andthep53/cell-cyclepathway.Uniqueesisofthisdisease.CancerRes;77(2);390–400.ó2016AACR.Introductiondeaths(1).UnlikeadultALL,mostpediatricALLpatientsrespondwelltoco

8、nventionalchemotherapy,andthe5-yearoverallsurvivalPediatricacutelymphoblasticleuke