Xiao Zejun, Zhang Jianjun, Zheng Shan, Li Changling, He Zugen, Cheng Shujun, Gao Yanning
Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
Zhonghua Yi Xue Za Zhi. 2002 Oct 25;82(20):1375-7.
To investigate the potential effects of three tumor suppressor genes located at chromosome 3p, FHIT, hMLH1 and VHL, in carcinogenesis of transitional cell carcinoma (TCC) of urinary bladder in Chinese.
PCR was used to examine the heterozygosity and loss of heterozygosity (LOH) of the 6 microsatellite polymorphic markers inside of or flanking to the three genes tumor suppressor genes FHIT, hMLHi, and VHL in TCC tissues of 40 cases.
The rates of heterozygosity and LOH were 55.0% (38/40) and 59.1% (22/38) for hMLH1 gene. The rates of heterozygosity and LOH were 90.0% (36/40) and 47.2% (17/36). The rate of heterozygosity of the two microsatellite polymorphic markers in the intron of FHIT gene, D2S1234 and D3S1300, were 70% (28/40) and 67.5% (27/40), The LOH rates of D2S1234 and D3S1300 were 46.4% (13/28) and 37% (10/27) respectively. The rate that at least one the these 2 microsatellite polymorphic markers was heterozygote was 95.0% (38/40), the rate that LOH occurred for at least one of them was 57.8% (22/38). The heterozygosity rate of D3S1561 and D3S1612, two microsatellite polymorphic markers linked to hMLH1 gene, were 42.5% (17/40) and 30% (12/40) respectively, the LOH rates for these two markers were 41.2% (7/17) and 75.0% (9/12) respectively, the rate that at least one of these two markers was heterozygote was 59.1% (13/22). The heterozygosity rate of D3S10368 and D3S1284, two microsatellite polymorphic markers linked to VHL gene, were 70% (28/40) and 47.5% (19/40) respectively, the LOH rates for these two markers were 42.8% (12/28) and 42.1% (8/19) respectively, the rate that at least one of these two markers was heterozygote was 90.0% (36/40). High frequencies of LOH were found in tumor suppressor genes FHIT, hMLH1 and VH. Only the LOH of D3S1284 was positively correlated with the pathological staging of TCC of urinary bladder (P < 0.05).
LOH in tumor suppressor genes FHIT, hMLH1 and VHL may play an important role in carcinogenesis of human urinary bladder, and may provide new approaches for early detection of TCC. Loss of VHK gene may be a late event of carcinogenesis of TCC.
探讨位于3号染色体上的三个抑癌基因FHIT、hMLH1和VHL在中国膀胱移行细胞癌（TCC）发生中的潜在作用。
采用聚合酶链反应（PCR）检测40例TCC组织中三个抑癌基因FHIT、hMLH1和VHL内部或侧翼6个微卫星多态性标记的杂合性和杂合性缺失（LOH）情况。
hMLH1基因的杂合率和LOH率分别为55.0%（38/40）和59.1%（22/38）。FHIT基因内含子中两个微卫星多态性标记D2S1234和D3S1300的杂合率分别为70%（28/40）和67.5%（27/40），D2S1234和D3S1300的LOH率分别为46.4%（13/28）和37%（10/27）。这两个微卫星多态性标记中至少有一个为杂合子的比例为95.0%（38/40），至少有一个发生LOH的比例为57.8%（22/38）。与hMLH1基因连锁的两个微卫星多态性标记D3S1561和D3S1612的杂合率分别为42.5%（17/40）和30%（12/40），这两个标记的LOH率分别为41.2%（7/17）和75.0%（9/12），这两个标记中至少有一个为杂合子的比例为59.1%（13/22）。与VHL基因连锁的两个微卫星多态性标记D3S10368和D3S1284的杂合率分别为70%（28/40）和47.5%（19/40），这两个标记的LOH率分别为42.8%（12/28）和42.1%（8/19），这两个标记中至少有一个为杂合子的比例为90.0%（36/40）。在抑癌基因FHIT、hMLH1和VHL中发现了高频率的LOH。仅D3S1284的LOH与膀胱TCC的病理分期呈正相关（P<0.05）。
抑癌基因FHIT、hMLH1和VHL中的LOH可能在人类膀胱癌发生中起重要作用，并可能为TCC的早期检测提供新途径。VHK基因的缺失可能是TCC发生的晚期事件。
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