结直肠腺瘤中的微卫星不稳定性类型

PDF(423 KB)

中国生物化学与分子生物学报 ›› 2003, Vol. 19 ›› Issue (06) : 799-806.

论文

结直肠腺瘤中的微卫星不稳定性类型

程蕾,王慧萍,黄琼,来茂德

作者信息 +

Different Types of Microsatellite Instability in Colorectal Adenomas

CHENG Lei 1) , WANG Hui ping 2) , HUANG Qiong 1) , LAI Mao de 1)*

Author information +

文章历史 +

摘要

应用微切割聚合酶链反应单链长度多态性 (PCR SSLP)的方法 ,检测 1 6个微卫星位点在 5 9例 6 2个结直肠腺瘤标本的微卫星不稳定性状态 .结果表明 :腺瘤 1 6个位点的总微卫星不稳定性(microsatelliteinstability ,MSI)发生率为 1 4 4 % ,MSI H所占的比率为 9 7% ;在 1 0例可以同时微切割得到腺瘤和癌变成分的病例中 ,腺瘤和癌变成分在每个微卫星位点的改变情况不完全相同 ,并且当在某一位点同时表现为阳性时 ,部分凝胶电泳的图像相同 ,而部分不同 ;在某些位点表现为癌变成分的异常条带泳动速度更快 ,说明序列比腺瘤中更短 ;MSI H与病人的年龄、性别、腺瘤发生部位和病理学亚型之间未见统计学差异 ,但MSI H组的平均年龄 (5 6 5 0± 1 1 38)低于MSI L组 (6 0 36±1 1 34) ,女性所占比率 (5 6 )明显高于男性 ,6例MSI H中无 1例组织学类型为管状腺瘤 ;各位点在MSI H组的MSI改变率明显高于MSI L组 ,在TGFβRⅡ (A) 1 0 、hMSH6、TCF4、BAT2 6等位点有明显差异 (P <0 0 5 ,其中BAT2 6的P <0 0 1 ) .可以推断 :在结直肠癌发生发展的早期即腺瘤阶段即可表现微卫星不稳定性 ;微卫星不稳定性可以随结直肠肿瘤的发展过程而发展 ,并且特定的微卫星位点的改变可能仅发生于肿瘤进程的特定阶段 ;在结直肠癌

Abstract

The MSI status of 16 microsatellite loci of 62 adenoma specimens from 59 patients were detected by means of manual microdissection PCR SSLP. The overall MSI rate of the 16 microsatellite loci was 14 4%, and the frequency of MSI H (microsatellite instability high frequency) was 9 7%. Both adenoma and carcinoma cells were obtained from 10 patients. The MSI status of adenoma and carcinoma at certain loci may be different; and at certain loci carcinoma showed faster shifting bands than adenoma, which meant a shorter microsatellite sequence in carcinoma; There were no significant differences of MSI H with respect to age and sex of patients, or the site and histological subtypes of the adenomas. MSI H patients were younger than MSI L patients (56 50±11 38 vs. 60 36±11 34) and more common in female (5/6) MSI H group was not tubular adenoma histologically; MSI alteration rates at these loci of TGFβRⅡ(A) 10 , hMSH6, TCF4, BAT26 in MSI H group were significantly higher than those in MSI low group ( P <0 05, and P <0 01 as to BAT26). It could be concluded that microsatellite instability existed even in the early stage of colorectal tumorigenesis. MSI could be dynamically changing with the progression of the colorectal tumors, and certain microsatellite alterations might occur only at certain stage of colorectal carcinogenesis. The difference between MSI H and MSI L groups existing in carcinoma is also seen in adenomas. MSI H and MSI L adenomas may be two types of colorectal adenomas.

导出引用

程蕾,王慧萍,黄琼,来茂德. 结直肠腺瘤中的微卫星不稳定性类型[J]. 中国生物化学与分子生物学报, 2003, 19(06): 799-806

CHENG Lei 1) , WANG Hui ping 2) , HUANG Qiong 1) , LAI Mao de 1)*. Different Types of Microsatellite Instability in Colorectal Adenomas[J]. Chinese Journal of Biochemistry and Molecular Biology, 2003, 19(06): 799-806

参考文献

1　KimKM ,SalovaaraR ,MecklinJP ,JarvinenHJ,AaltonenLA ,ShibataD .PolyAdeletioninhereditarynonpolyposiscolorectalcancer:mutationsbeforeagatekeeper.AmJPathol,2002,160:1503～1506 2　SchmutteC ,FishelR .Genomicinstability:firststeptocarcinogenesis.AnticancerRes,1999,6:4665～4696 3　来茂德.人实体瘤中的微卫星不稳定性.国外医学遗传学分册(LaiMao de.Microsatelliteinstabilityinhumansolidtumors.ForeignMedicalSciences:Genetics),1999,22:306～312 4　HonchelR ,HallingKC ,ThibodeauSN .Genomicinstabilityinneoplasia.SeminCellBiol,1995,6:45～52 5　ShibataD ,PeinadoMA ,IonovY ,MalkhosyanS ,PeruchoM .Genomicinstabilityinrepeatedsequencesisanearlysomaticeventincolorectaltumorigenesisthatpersistaftertransformation.NatGenet,1994,6:373～281 6　BhattacharyyaNP ,SkandalisA ,GaneshA ,GrodenJ,MeuthM .Mutatorphenotypeinhumancolorectalcarcinomacelllines.ProcNatlAcadSciUSA ,1994,91:6319～6323 7　ThibodeauSN ,FrenchAJ,CunninghamJM ,TesterD ,BurgartLJ ,RochePC ,McDonnellSK ,SchaidDJ,VockleyCW ,MichelsVV ,FarrGHJr,O’ConnellMJ .Microsatelliteinstabilityincolorectalcancer:differentmutatorphenotypesandtheprincipalinvolvementofhMSH1.CancerRes,1998,58:1713～1718 8　BolandCR ,ThibodeauSN ,HamiltonSR ,SidranskyD ,EshlemanJR ,BurtRW ,MeltzerSJ,RodriguezBigasMA ,FoddeR ,RanzaniGN ,SrivastavaS .Anationalcancerinstituteworkshoponmicrosatelliteinstabilityforcancerdetectionandfamilialpredisposition:developmentofinternationalcriteriaforthedeterminationofmicrosatelliteinstabilityincolorectalcancer.CancerRes,1998,58:5248～5257 9　YashiroM ,CarethersJM ,LaghiL ,SaitoK ,SlezakP ,JaramilloE ,RubioC ,KoizumiK ,HirakawaK ,BolandCR .Geneticpathwaysintheevolutionofmorphologicallydistinctcolorectalneoplasms.CancerRes,2001,61:2676～2683 10　KonishiM ,KikuchiYanoshitaR ,TanakaK ,MuraokaM ,OndaA ,OkumuraY ,KishiN ,IwamaT ,MoriT ,KoikeM ,UshioK ,ChibaM ,NomizuS ,KonishiF ,UtsunomiyaJ,MiyakiM .Microsatelliteinstabilityincolorectaladenomas.Gastroenterology,1997,112:1515～1519 11　TsaoJL ,TavareS ,SalovaaraR ,JassJR ,AaltonenLA ,ShibataD .Colorectaladenomaandcancerdivergence;evidenceofmultilineageprogression.AmJPathol,1999,154:1825～1830 12　RashidA ,ZahurakM ,GoodmanSN ,HamiltonSR .GeneticepidemiologyofmutatedK rasproto oncogene,alteredsuppressorgenes,andmicrosatelliteinstabilityincolorectaladenomas.Gut,1999,44:826～833 13　PramlC ,FinkeLH ,HerfarthC ,SchlagP ,SchwabM ,AmlerL .Deletionmappingdefinesdifferentregionsin1p34.2 pterthatmayharborgeneticinformationrelatedtohumancolorectalcancer.Oncogene,1995,11:1357～1362 14　HoangJM ,CottuPH ,ThuilleB ,SalmonRJ,ThomasG ,HamelinR .Bat26,aindicatorofthereplicationerrorphenotypeincolorectalcancersandcelllines.CancerRes,1997,57:300～303 15　MarkowitzS ,WangJ,MyeroffL ,ParsonsK ,SunL ,LutterbeughJ,FanRS ,ZborowskaE ,KinzlerKW ,VogelsteinB .InactivationofthetypeⅡTGFβreceptorincoloncancercellswithmicrosatelliteinstability.Science,1995,268:1336～1338 16　SpirioL ,NelsonL ,WardK ,BurtR ,WhiteR ,LeppertM .ACA repeatpolymorphismclosetotheadenomatouspolyposiscoli(APC)geneoffersimproveddiagnostictestingforfamilialAPC .AmJHumGenet,1993,52:286～296 17　SpirioL ,JoslynG ,NelsonL ,LeppertM ,WhiteR .ACArepeat3070KBdownstreamfromtheadenomatouspolyposiscoli(APC)gene.NucleicAcidsRes,1991,19:6348 18　YamamotoH ,SawaiH ,PeruchoM .Frameshiftsomaticmutationsingastrointestinalcancerofthemicrosatellitemutatorphenotype.CancerRes,1997,57:4420～4426 19　JassJR ,DoKA ,SimmsLA ,IinoH ,WynterC ,PillaySP ,SearleJ,RadfordSmithG ,YoungJ ,LeggettB .MorphologyofsporadiccolorectalcancerwithDNAreplicationerrors.Gut,1998,42:673～639 20　LaihoP ,LaunonenV ,LahermoP ,EstellerM ,GuoM ,HermanJG ,MecklinJP ,JarvinenH ,SistonenP ,KimKM ,ShibataD ,HoulstonRS ,AaltonenLA .Low levelmicrosatelliteinstabilityinmostcolorectalcarcinomas.CancerRes,2002,62:1166～1170 21　KambaraT ,MatsubaraN ,NakagawaH ,NotoharaK ,NagasakaT ,YoshinoT ,IsozakiH ,SharpGB ,ShimizuK ,JassJ,TanakaN .Highfrequencyoflow levelmicrosatelliteinstabilityinearlycolorectalcancer.CancerRes,2001,61:7743～7746 22　StarostikP ,HermelinkHK .Diagnosisofmicrosatelliteinstability positivecolorectalcancer.MolD

PDF(423 KB)

112

Accesses

Citation

Detail

段落导航

摘要
Abstract
关键词
Key words
引用本文
参考文献

收稿日期	修回日期	出版日期
2003-12-20	2003-12-20	2003-12-20
发布日期
2003-12-20

选择文件类型/文献管理软件名称

选择包含的内容

摘要

Abstract

关键词

Key words

引用本文

{{custom_sec.title}}

{{custom_sec.title}}

参考文献

{{custom_fnGroup.title_cn}}

脚注

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

摘要

Abstract

关键词

Key words

引用本文

{{custom_sec.title}}

{{custom_sec.title}}

参考文献

{{custom_fnGroup.title_cn}}

脚注