人膀胱移行细胞癌染色体9p21.3-9p23杂合性缺失作图

目的　研究并确定人膀胱移行细胞癌染色体 9p2 1.3 -9p2 3区域杂合性缺失发生率和最小缺失区域 ,为寻找与克隆膀胱移行细胞癌相关的抑癌基因提供线索。方法　选取 7个微卫星多态性标记 (其中 6个位于 9p2 1.3 -9p2 3 ,另 1个位于 9q3 4作为对照 ) ,对 2 4例膀胱移行细胞癌组织及其对应的外周血淋巴细胞进行核素标记的聚合酶链反应和聚丙烯酰胺变性凝胶电泳。分析 9p2 1.3 -9p2 3区各微卫星位点杂合性缺失的发生情况及其与病理分期分级的关系。 结果　 2 4例膀胱癌中的 2 0例 (83 .3 % )存在至少 1个微卫星位点的杂合性缺失。在 9p2 1.3 -9p2 3区域的 6个位点中 ,杂合性缺失率最高的为 9p2 3的D9S2 85 ,达66.7%(8/12 ) ;其次为 9p2 1的D9S1846,达 5 4.5 % (6/11)。位于 9q3 4.12的D9S182 1的杂合性缺失率为 5 4.5 % (6/11) ,而且在发生杂合性缺失的 6个病例中 ,有 5个被证明为部分染色体片段的缺失。结论　在 9p2 1.3 -9p2 3区域 ,可能至少存在 2个与膀胱移行细胞癌相关的候选抑癌基因 ,分别位于D 9S2 85和D9S1846附近

Mapping the Loss of Heterozygosity on Chromosome 9p21.3-9p23 in Transitional Cell Carcinoma of Human Urinary Bladder

Objective To explore the candidate tumor suppressor gene(s) associated with the malignancy,the investigation was carried out to determine the minimal deletion regions on chromosome 9p21.3 9p23 in transitional cell carcinoma of human urinary bladder.Methods With 7 microsatellite markers,the loss of heterozygosity was examined on 24 surgical specimens of transitional cell carcinoma tissue and the corresponding lymphocytes by PCR and polyacrylamide gel electrophoresis.Statistical analysis of the relationship between the frequency of loss of heterozygosity and pathological grade and stage of the tumors was performed.Results Among the 24 samples,20(83.3%) were detected with loss of heterozygosity in at least one of the 6 loci in 9p21.3 9p23.The most frequent loss of heterozygosity locus was D9S285(66.7%,8/12),followed by D9S1846(54.5%,6/11).The frequency of loss of heterozygosity at D9S1821 on 9q34 was 54.5%(6/11).Conclusion There might be,at least,two tumor suppressor genes associated with carcinogenesis of transitional cell carcinoma of urinary bladder,harboring in 9p21.3 9p23,around D9S285 and D9S1846,respectively.