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目的探讨膀胱癌克隆演变(clonal evolution)过程中遗传学机制。方法分别利用4个位于染色体9p21区和17p13区上的具有多态性的微卫星标记物分析18例膀胱癌病人原发癌及相应转移灶中等位基因的缺失或保留方式。利用显微切割技术在保存的石蜡包埋组织中获取基因组DNA。结果在原发癌和转移灶中总的等位基因缺失频率分别为78%(14/18)和89%(16/18);原发癌和转移灶在各位点D9S161的缺失频率为86%和100%,D9S171为67%和67%,IFNA71%和71%,TP5380%和80%。在18病例中,16例(89%)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2例(11%)则显示不一致的等位基因缺失。这2例原发癌表现为等位基因保留而在相应转移灶则为缺失。结论膀胱癌在原发癌及相应转移灶遗传组成上有相当一致性;当转移癌的原发癌不能确定来源时,位点D9S161,D9S171,IFNA和TP53的杂合性缺失可能作为膀胱癌的标志物。
Objective To investigate the genetic mechanism of clonal evolution in bladder cancer. Methods Four microsatellite markers with polymorphisms on chromosome 9p21 and 17p13 were used to analyze the deletion or retention of alleles in 18 cases of primary carcinoma and corresponding metastasis of bladder cancer. Genomic DNA was obtained in preserved paraffin-embedded tissue using microdissection. Results The total allele deletion frequency was 78% (14/18) and 89% (16/18) in primary cancer and metastasis respectively. The frequency of deletion of D9S161 in primary cancer and metastasis was 86% And 100%, D9S171 67% and 67%, IFNA 71% and 71%, TP5380% and 80%. Of the 18 cases, 16 (89%) showed the same pattern of allelic loss or retention at all sites in the primary cancer and corresponding metastases, while the other 2 (11%) showed inconsistent alleles Gene deletion. These 2 cases of primary cancer showed allele retention and loss in the corresponding metastasis. CONCLUSIONS: Bladder cancer is quite consistent in the genetic composition of primary and corresponding metastases. The loss of heterozygosity at loci D9S161, D9S171, IFNA and TP53 may be used as a marker of bladder cancer when the primary cancer of metastatic carcinoma can not be identified landmark.