人膀胱移行细胞癌染色体17p13区域杂合性缺失精细作图

目的　明确染色体 17p13区域等位基因杂合性缺失 (LOH)在人膀胱移行细胞癌 (TCC)中的发生频率和最小缺失区域 ,为膀胱TCC相关抑癌基因的定位克隆提供线索。方法　应用位于17p13区域的 13个微卫星标记 ,对 4 4例膀胱TCC患者手术切除的癌组织进行LOH分析 ,并探讨各微卫星标记LOH与病理分级、分期的关系。结果　 4 4例患者中 ,35例 (79 5 % )的膀胱TCC组织中存在至少 1个微卫星标记的LOH。缺失频率最高的微卫星标记是位于 17p13 2的D17S5 13,达 4 1 4 % (12 /2 9) ;其次为位于 17p13 3的D17S130 8,为 4 0 5 % (17/ 4 2 ) ;最低为位于 17p13 1的D17S2 6 1,为 14 3% (4/2 8)。LOH主要集中于三个区域 :位于 17p13 3的D17S6 95～D17S130 8,位于 17p13 2的D17S15 33～D17S831,以及位于 17p13 1区域的TP5 3。所检测微卫星标记中仅TP5 3的LOH与膀胱TCC病理分级(χ2 =5 10 4 ,P <0 0 5 )和分期 (χ2 =5 382 ,P <0 0 5 )呈正相关。结论　在 17p13区域除TP5 3基因以外 ,还可能存在两个与膀胱TCC相关的抑癌基因 ,分别位于 17p13 3的D17S6 95～D17S130 8和17p13 2的D17S15 33～D17S831。TP5 3的LOH是膀胱TCC发展的晚期事件 ,而 17p13 3和 17p13 2区域的LOH则可能是膀胱TCC发生的早期事件

Loss of heterozygosity fine mapping of chromosome 17p13 in transitional cell carcinoma of human urinary bladder

OBJECTIVE: To determine the frequency and common deletion region of allelic losses on chromosome 17p13 in transitional cell carcinoma (TCC) of human urinary bladder so as to provide clues for isolation of candidate tumor suppressor genes associated with TCC of urinary bladder. METHODS: Loss of heterozygosity (LOH) analysis was made on 44 samples of surgically resected primary TCC by using 13 microsatellite markers to map the regions frequently deleted on chromosome 17p13. The relationship between the LOH in each locus and pathological grade and stage was analyzed. RESULTS: Out of the 44 samples, 35 (79.5%) showed allelic loss in at least one of the 17p13 loci. The highest frequency of LOH (41.4%, 12/29) was at D17S513 in 17p13.2, the second highest frequency of LOH (40.5%, 17/42) was at D17S1308 in 17p13.3, and the lowest (14.3%, 4/28) was at D17S261 in 17p13.1. The most frequent LOH loci were mainly located in three regions: D17S695-D17S1308 in 17p13.3, D17S1533-D17S831 in 17p13.2, and TP53 in 17p13.1. Among them only the LOH frequency of TP53 locus was positively correlated to the grade (chi(2) = 5.104, P < 0.05) and stage (chi(2) = 5.382, P < 0.05) of TCC of unrinary bladder. CONCLUSION: In 17p13 region, except for TP53 gene, still exist two candidate tumor suppressor genes located in D17S695-D17S1308 and D17S1533-D17S831 involved in the carcinogenesis of TCC of urinary bladder. LOH of TP53 locus may be one of the later events in TCC, and LOH in 17p13.3 and 17p13.2 may be the early events of TCC of uninary bladder.