Genomic instability analysis of urine sediment versus tumor tissue in transitional cell carcinoma of the urinary bladder.
Microsatellite alterations are a common feature of neoplastic cells. Our study aimed to compare the profile of microsatellite DNA alterations in tumor tissue and urine sediment at 12 selected microsatellite loci in transitional cell carcinoma of the bladder, and to determine which of the 12 markers or combination of markers has potential for the non-invasive diagnosis of bladder cancer. DNA alterations were examined using microsatellite markers on chromosomes 2p, 3p, 8p, 9p, 9q, 12q, 13q, 17p and 18q in 38 patients, including 12 with superficial Ta/T1 and 26 with muscle invasive T2-T4 bladder tumors. Microsatellite instability was a rare event in comparison with loss of heterozygosity and was related to a low rate of defects in mismatch repair genes. The sensitivity of microsatellite analysis was 75% (9/12) for Ta/T1 tumors and 69% (18/26) for T2-T4 tumors. Two tetranucleotide markers, D9S242 and D9S252, when combined, displayed microsatellite alterations in 59% (16/27) of microsatellite analysis-positive patients. DNA alterations were not detected in 21 non-tumor specimens. Twenty of 51 (39%) tumor DNA alterations were re-detected in urine sediments, and 7 alterations found in urine sediments were not found in the corresponding tumor specimens. No association was found between the DNA alterations and any of the prognostic parameters. However, the overall survival correlated with microsatellite alterations (P=0.04, log-rank test). These data suggest that markers at tetranucleotide repeats on chromosome 9q have particular diagnostic potential in bladder cancer. Moreover, microsatellite analysis is suitable for the selection of patients with a less favorable outcome.
Turyn
Jacek
J
Department of Biochemistry, Medical University of Gdansk, Poland.
Matuszewski
Marcin
M
Schlichtholz
Beata
B
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004273:DNA, Neoplasm / Q000652:urine*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000652:urine
D004273:DNA, Neoplasm