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1、肾透明细胞癌遗传聚类的阵列比较基因组杂交技术：DNA甲基化与肾癌患者预后之间的关系（GeneticClusteringofClearCellRenalCellCarcinomaBasedonArray-ComparativeGenomicHybridization:ItsAssociationwithDNAMethylationAlterationandPatientOutcome）AbstractPurpose:Theaimofthisstudywastoclarifygeneticandepig
2、eneticalterationsoccurringduringrenalcarcinogenesis.ExperimentalDesign:Copynumberalterationswereexaminedbyarray-basedcomparativegenomichybridizationanalysisusinganarrayharboring4,361bacterialartificialchromosomeclones,andDNAmethylationalterationsonCpGi
3、slandsofthep16,humanMutLhomologue1,vonHippel-Lindau,andthrombospondin1genesandthemethylatedintumor(MINT-1,MINT-2,MINT-12,MINT-25,andMINT-31)cloneswereexaminedin51clearcellrenalcellcarcinomas(RCC).Results:Byunsupervisedhierarchicalclusteringanalysisbase
4、doncopynumberalterations,clearcellRCCswereclusteredintothetwosubclasses,clustersA(n=34)andB(n=17).CopynumberalterationswereaccumulatedinclusterB.Lossofchromosome3pandgainof5qand7werefrequentinbothclustersAandB,whereaslossof1p,4,9,13q,and14qwasfrequento
5、nlyinclusterB.TheaveragenumberofmethylatedCpGislandsinclusterBwassignificantlyhigherthanthoseinclusterA.ClearcellRCCsshowinghigherhistologicgrades,vascularinvolvement,renalveintumorthrombi,andhigherpathologicstageswereaccumulatedinclusterB.Therecur-ren
6、ce-freeandoverallsurvivalratesofpatientsinclusterBweresignificantlylowerthanthoseofpatientsinclusterA.Multivariateanalysisrevealedthatgeneticclusteringwasapredictorofrecurrence-freesurvivalandwasindependentofhistologicgradeandpathologicstage.Conclusion
7、s:ThisgeneticclusteringofclearcellRCCissignificantlyassociatedwithregionalDNAhypermethylationandmaybecomeaprognosticindicatorforpatientswithRCC.Keywords:RCCGeneticClusteringArray-ComparativeGenomicHybridizationDNAMethylationAlterationPatientOutcome摘要肾细
8、胞癌（RCC）是最常见的恶性成人肾脏肿瘤，经常影响工作年龄成人的生活。在一般情况下，肾细胞癌在早期阶段由肾切除可以治愈的。然而，一些肾细胞癌的即使已完全切除仍易复发和转移至远处器官。转移肾细胞癌抵抗传统的化疗和放疗和有一个很差的预后，最近，治疗肾癌已成立了免疫疗法和已开发了新型靶向制剂。然而，除非密切随访早期诊断的复发或转移肿瘤，任何有效性治疗是非常严格的限制。因此，协助密切跟进肾切除和仍处于复发和转移风险的患者，预后指标应建立在了解肾癌发生的分子机制基础上。虽然肾细
