胰腺神经内分泌肿瘤的全基因组图谱.ppt课件模板文档，格式 ppt，大小 4.17 MB，共约33页。以下是概述： PanNETs-PanNETs-胰腺神经内分泌肿瘤胰腺神经内分泌肿瘤的全基因组图谱的全基因组图谱nature_PPTnature_PPT课课件件PanNETs•Pancreaticneuroendocrinetumours(PanNETs)：thesecondmostcommonepithelialneoplasmofthepancreasandhaveamortalityrateof60%.•WHOclassification：lowgrade(G1),intermediategrade(G2),highgrade(G3)•G3tumoursareinvariablylethal•90%ofPanNETsaregradeG1orG2PanNETs•PanNETs:sporadic,threehereditarysyndromes:multipleendocrineneoplasiatype1(MEN-1),vonHippel-Lindausyndrome(VHL),andoccasionallytuberoussclerosiscomplex(TSC)•MEN-1:35%ofPanNETs•mTORsignalling:14%ofpatients,Everolimus(advancedPanNET)•apoptoticregulatorDAXXorthechromatinmodifierATRX:40%ofPanNETs,promotealternativelengtheningoftelomeres(ALT,端粒替代延长机制)andchromosomalinstabilityMutationalmechanismsinPanNETMutationalmechanismsinPanNETMutationalmechanismsinPanNETMUTYH:•Anovelmutationalsignature,composedofG:C>T:Atransversions,predominatedinfivePanNETs(range0.2–4.2mutationsperMb),whichboreaknownpathogenicornovelinactivatinggermlinemutationinthebase-excision-repairgeneMUTYH,coupledwithlossofheterozygosity.•ThismutationalsignatureorpatternofbiallelicMUTYHinactivationwasnotobservedin100pancreaticductaladenocarcinomas.MutationalmechanismsinPanNET•MUTYH:3/62•Italiancohort,themostcommonMAP-linkedvariantsinpopulationsofEuropeanorigin•80familieswithMAPfromItalyandGermany•Thesedatasuggestthat,inadditiontopredisposingtocolonic,gastricandavarietyofnon-gastrointestinalcancers,MUTYHdeficiencyplaysaroleinPanNET.MutationalmechanismsinPanNETMutationalmechanismsinPanNETMutationalmechanismsinPanNET•Clustersofbreakpoints:ninetumours(9%),structuralvariationsandcopy-numberchangesconsistentwithchromothripsis.•Fouroftheseninetumourshadrecurrentcatastrophicrearrangementsonchromosome11q,allinvolving11q13,andtwooftheserearrangementsledtolossofMEN1.•TP53:noTP53mutationswerepresentinPanNETs.Germlinemutations•ThediscoveryofgermlinedeleteriousmutationsinMUTYHandBRCA2promptedustoscreenthegermlinesofallpatientsformutatio...
