胶质瘤基因突变笔记PPT课件.ppt

Imaginggenomicmappinginglioblastoma ShenXudong 1 Amongadultcentralnervoussystemmalignancies glioblastoma GBM isthemostcommonprimarymalignantbraintumor accountingfor52 ofallfunctionaltissuebraintumorcasesand20 ofallintracranialtumors intheUnitedStates在成人中枢神经系统恶性肿瘤中 胶质母细胞瘤 GBM 是最常见的原发性恶性肿瘤 占所有脑功能组织肿瘤的52 和所有颅内肿瘤的20 2 thebestcurrentlyavailablemultimodaltreatmentremainssurgicalresectionfollowedbyconcomitantandadjuvantradiationtherapyandtemozolomidetherapy 目前GBM最合适的综合治疗仍然是手术切除后进行辅助放射治疗和替莫唑胺治疗 3 despiterecentadvancesinnovelsequencingandmicroarraytechnologiesthathaveledtoprofounddiscoveriesandabetterunderstandingofDNA andRNA basedgenomicalterationsincancerandtheavailabilityofthesedatatothescientificcommunity littleprogressinGBMtherapyhasbeenmade尽管新型测序和基因芯片技术的最新进展取得了重大发现和更好地理解DNA和RNA为基础的基因组在癌症中的改变和在科学界对这些数据的可用性 但胶质母细胞瘤的治疗取得的进展并不大 4 TheidentificationofmicroRNA miRNA andgeneexpressionprofilesinpatientswithdistinctandclinicallyrelevanttumorgenotypesandphenotypeswilluncoverpotentialnewtherapeutictargetsandmolecularpathways identifycandidatepatientsfortargetedtherapy predictapatient searlyresponseorfailuretorespondtotherapy andprovideinvaluableprognosticinformation 患者微RNA 基因表达谱 临床相关的肿瘤基因型及表型的识别将发现潜在的新的治疗靶点和分子途径 识别候选病人进行有针对性的治疗 预测病人的早期反应或失败响应治疗 并提供宝贵的预后信息 5 Theimportanceofepigeneticsandchangesingeneexpress miRNAlevels andthesurroundingtumormicroenvironmentisincreasinglybeingrecognized 表观遗传学和基因表达的改变 miRNA水平及肿瘤周围微环境的重要性越来越被人们认识 6 alterationsinepigeneticprocessescanleadtogeneticmutations andgeneticmutationsinepigeneticregulatorsresultinanalteredepigenome 表观遗传过程的改变可以导致基因突变 基因突变的表观遗传调节结果是基因组突变 7 TheprognosticandpredictivevaluesofthemethylationstatusoftheMGMTpromoterandIDHstatushaveshiftedtheGBMclassificationtoamolecular basedclassificationthathasclinicalimplicationsandrelevance MGMT启动子的甲基化状态和IDH突变状态的预后和预测值价值已经改变了胶质母细胞瘤的分类至分子水平 具有临床意义和相关性 8 However asofyet nomolecularprofiling basedGBMclassificationhassufficientlyhighclinicalrelevancefortheselectionofdifferenttherapeuticstrategiesandthedeterminationofpatientoutcome 然而 迄今为止 在针对不同的治疗策略的选择和患者预后的判断方面 还没有基于分子基础的GBM的分类 9 HypermethylationoftheMGMTpromotercausesepigenetic mediatedsilencingofMGMTandhasbeenconfirmedinmultipleclinicaltrialsasanimportantpredictivegenomicbiomarkerinthecontextofalkylatingagentssuchastemozolomide itisalsooneofthemostimportantprognosticfactorsforprogression freesurvivalandoverallsurvivalinpatientswithGBM IDH1mutationscanhelpdifferentiateprimaryfromsecondaryGBMsandportendabetterprognosisinpatientswhoharborthesemutations 10 MGMT启动子甲基化引起的表观遗传介导的MGMT