前列腺癌等位基因失衡

摘要

目的 了解前列腺癌克隆演变(clonal evolution)过程中遗传学机制. 方法 采用激光显微切割技术从保存的石蜡包埋组织中获取基因组DNA;利用6个位于染色体8p12-21、8p22、17q21上的具有多态性的微卫星标记,对25例患者原发癌及相应转移灶中等位基因的缺失或保留进行分析. 结果 在24例可供信息的病例中,14例(58%)在原发癌及相应转移灶中所有位点均表现为相同的等位基因缺失或保留模式,而另外10例(42%)则显示不一致的等位基因缺失.这10例中有5例原发癌表现为等位基因保留而在相应转移灶则为缺失,另外5例在一个或一个以上的位点表现为原发癌等位基因缺失而在相应转移灶保留. 结论 前列腺癌在原发癌及相应转移灶遗传组成上的差异可能与其内在异质性、整体遗传不稳定性及克隆差异有关.%Objective To better understand the genetic basis of the elonal evolution of prostate carcinoma. Methods DNA sampies were prepared by Laser microdissection(LCM). The pattern of allelic loss in matched primary and metastatic prostatic adanocarcinomas from 25 patients were analyzed by using six oligonueleotide primer pairs for the microstatdlite DNA markers on chromosome8p12-21,on chromoseme 8p22 and D17S855 on chromosome 17q21. Results The overall frequencies of alldic imbalance were79% in primary tumors and 88% in paired metastases. Of 24 informative cases, 14 cases(58% )showed the same pattern of allelic lossor retention in marched primary and metastatic tumor at all marker loci,and 10 cases(42%)showed discordant aUelic loss. Five patients showed allelic loss in at least one genetic marker in the metastatic tumor but not in its matched primary tumor. Five patientsdisplayed loss in one or more marker loci in a primary tumor but not in the matched metastases. Conclusion These data suggestthat different patterns of allelic deletion may be acquired during cancer progression to metastasis. The difference in genetic compositionbetween primary prostate carcinoma and its metastasis may be related to intrinsic cancer heterogeneity,overaU genetic instability,andclonal divergence.