[Loss of heterozygosity of tumor suppressor genes at chromosome 3p in transitional cell carcinoma of urinary bladder].
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Xiao
Zejun
Z
Department of Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
Zhang
Jianjun
J
Zheng
Shan
S
Li
Changling
C
He
Zugen
Z
Cheng
Shujun
S
Gao
Yanning
Y
D017766:Acid Anhydride Hydrolases; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008025:Ligases / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D008025:Ligases; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099170:Bis(5'-adenosyl)triphosphatase; C501486:MLH1 protein, human; C497446:VHL protein, human