膀胱癌及其正常组织染色体缺失研究及其临床意义

Allelic loss of heterozygosity in normal urthelium of patients with bladder cancer

目的探讨膀胱癌患者9号染色体及p53等位基因的杂合性缺失(LOH)与膀胱移行细胞癌(TCC)形成、进展之间的关系及其在早期诊断膀胱癌及复发检测中的价值。方法选取9、17号染色体的5个微卫星位点D9S283、D9S303、D9S304、D9S1751和TP53,采用特异引物进行PCR扩增及变性聚丙烯酰胺凝胶电泳-硝酸银染色方法对40例TCC患者手术切除的癌组织及癌旁正常组织进行微卫星分析。结果 40例癌组织中,36例(90%)分别有1～5个微卫星位点发生LOH,其中微卫星改变发生最高的位点是TP53,发生率为62.5%,其次为D9S283,发生率为42.5%。结论 9、17号染色体上的5个微卫星位点LOH参与了膀胱癌的发生,通过检测这5个位点的LOH,可以为膀胱癌的早期诊断提供一定的线索。

Objective To investigate the relationship between loss of heterozygosity（LOH） of allele loci on chromosomes 9 and P53 in Chinese and development of transitional cell carcinoma（TCC） of urinary bladder.Methods LOH was studied in the tumor tissues of 40 patients,with their normal tumor-adjacent bladder tissues as control,by means of PCR amplification of 5 polymorphic microsatellite DNA loci D9S283,D9S303,D9S304,and D9S1751 on chromosome 9 and TP53.Following silver staining,8% denaturing polyacrilamide gel electrophoresis was performed.Results 36（90%） TCCs showed LOH at one or more loci,and 26 TCCs showed LOH at 2 loci.There was no significant difference between superfacial TCC and invasive TCC at these loci.Conclusion LOH on chromosome 9 might be an early event of the genesis of TCC of bladder,and LOH on p53 might be related with progression of TCC.Racial difference may contribute to different LOH on chromosome 9 and p53 between Chinese people and others.The combination of markers D9S283,D9S303,D9S304,D9S1751 and TP53 enable us to detect 36 out 40 of bladder cancers（90%）;This panel might be chosen for microsatellite analysis in bladder cancer of Chinese.