抑癌基因DCC和MCC在大肠癌中的变化

ASTUDYONTHECHANGESOFDCCANDMCCGENESINCOLORECTALCARCINOMAANDADENO

为了探讨ＤＣＣ和ＭＣＣ在中国人大肠腺瘤和大肠癌中的变化及其与大肠腺癌的分级、分期和大肠腺瘤的分级之间的关系，对３０例大肠腺瘤和３３例大肠癌患者用Ｓｏｕｔｈｅｒｎ杂交法检测了ＤＣＣ基因的突变和用聚合酶链反应（ＰＣＲ）方法检测了ＭＣＣ的杂合缺失（ＬＯＨ）。结果为：在大肠腺瘤患者中，仅在重度不典型增生者中能检出ＤＣＣ的突变；在３３例大肠癌中检出７例突变，且随分化的减少和分期的增加而有频度增加的趋势。３０例腺瘤中有９例检出有ＭＣＣ的ＬＯＨ，其中轻、中、重度不典型增生者分别有２、３及４例；在３３例大肠癌中检出１８例ＭＣＣ的ＬＯＨ，且其发生的频度有明显的随分级、分期的严重而增加的趋势。结论：ＤＣＣ的变化可定位于腺瘤的中、晚期阶段；ＭＣＣ的变化可定位于正常组织与腺瘤之间，且与腺瘤至癌的演变有一定关联；以上结果支持大肠癌的发生、发展是一个多基因变化的过程这一学说。

Bothdeletedincolorectalcarcinoma(DCC)andmutatedincolorectalcarcinoma(MCC)genesarenewlyfoundtumoursuppressergenesincolorectalcarcinoma.InthisstudymutationsofDCCgeneandlossofheterozygosity(LOH)ofMCCgeneweredetectedwithSouthernblotandPCRmeth-odsrespectively.Thestudyconsistedof30casesofcolorectaladenoma(10withmild,10withmoderateand10withseveredysplasia)and33casesofcolorectalcarcinoma(13highly,10moderatelyand10poorlydiferentiated,meanwhile9inDukesA,10inBand14inCstage).Theirpairednormalcolorec-talmucosaservedascontrol.Theresultswereasfolows:mutationofDCCwasnotfoundinanyspeci-menwithnormalmucosaorwithadenomaofmildandmoderatedysplaaia,whileitwasfoundinoneofthosewithseveredysplasia.MutationofDCCwas,however,foundin7ofthe33specimenswithcarci-nomaandtherewasacorrelationbetweenthepositiverateandthediferentiationorstagingofthecarci-noma.LOHofMCCwasnotfoundinnormalmucosa,butitwasfoundin2/10,3/10and4/10oftheadenomaspecimenswithmild,moderateandseveredysplasiarespectively.18/33ofthecarcinomaspec-imenswasfoundtohaveLOHofMCCandtherewasalsoacorelationbetwenthepositiverateandthediferentiationorstagingofthecarcinoma.Theseresultssuggestthatthefrequencyofmultiplegenechangesincreasewithpoordiferentiationandincreasedstagingofcolorectalcarcinoma.