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1、中华实验外科杂志2004年10月第21卷第10期 ChinJExpSurg,October2004,Vol21,No.10·1209··实验研究·散发性结、直肠癌APC基因杂合缺失和突变的研究叶建新 许东坡 李心翔 【摘要】 目的 研究中国人散发性结、直肠癌中APC基因的失活形式和规律。方法 应用聚合酶链反应2单链构象多态性分析(PCR2SSCP)、DNA直接测序及微卫星标记PCR2LOH分析方法,检测分析40例散发性结直癌APC基因的突变和杂合缺失。结果40例结、直肠癌中有31例检测到APC基因改变:双次打击24例(其中LOH加突变15例,双突变9例),单个突变而无LOH5例,仅有LO
2、H而无突变2例。APC基因突变率及杂合缺失率与肿瘤部位,肿瘤分化程度及Duke’s分期等无关。结论APC基因改变与中国人散发性结直肠癌的发生有关。在大多数的中国人散发性结直肠癌的发生中,需要APC基因的双打击致功能完全失活,而且LOH加突变可能是其主要形式。在肿瘤获得恶性表型后,其进展及预后与APC基因杂合缺失与否无关。【关键词】 结直肠癌; 基因表达; 突变StudyontheAPCgenelossofheterogygosityandmutationinsporadiccolorectalcarcinomasYEJian2xin,XUDong2po,LIXin2xiang.Depart
3、mentofOncologicSurgery,TheFirstAffiliatedHospitalofFujianMedicalUniversity,Fuzhou350001,China【Abstract】ObjectiveToinvestigatethelawsandpatternofAPCinactivation(mutationand/orLOH)inChinesesporadiccolorectalcarcinomas.MethodsFortycasesofsporadiccolorectalcarcinomaswereanalyzedbyPCR,single2strandconf
4、ormationpolymorphisim(SSCP)analysis,aswellasAPCgenePCR2LOHassay.ResultsOfthe40colorectalcarcinomas,31(77.5%)casesshowedevidenceofAPCmutationand/orallelicloss.In24of31(77.4%)ofthesecarcinomas,2hitswerefound.Ofthe24cas2es,15(62.5%)showedalleliclossplusmutation,9(37.5%)harboredtwomutations.Intheremai
5、ning7cases,onlyoneAPCmutationoralleliclosswasfoundineachcase.TheoverallfrequencyofalleliclossatAPCwas42.5%(17of40carcinomas).Thirty-eightmutationsidentifiedin29caseswereallfoundinexon15.Ofthese38mutations,29(76.3%)occurredintheMCR,3infragment152B,3infragment152E,2infragment152F,1infragment152D.Fiv
6、emutationsin4caseswereprovedbyDNAsequenc2ing.Ofthese5mutations,2wereonebasepairinsertions,1wastwobasepairsdeletion.Alloftheinser2tionsanddeletionproducedaframeshiftthatwouldtruncatetheprotein.Theothertwowerenonsensemutationsthatwouldalsotruncatetheprotein.APCchangeswerecorrelatedwithclinicopatholo
7、gicalvari2ables,suchastumorsite,tumordifferentiationandDuke’sstage.ConclusionLOHplusmutationmightbethemainpatternoftheinactivationoftheAPCgene,andinvolvedinmostsporadiccolorectalcarcino2genesis.Aftermalignantcolo
