Deletion mapping implicates two tumor suppressor genes on chromosome 8p in the development of bladder cancer.
Chromosome 8 loss of heterozygosity (LOH) in cancer of the urinary bladder is associated with high tumour grade and stage. We have screened 193 cases of transitional cell carcinoma (TCC) of the bladder using 30 microsatellite polymorphisms on chromosome 8. Forty three cases (22%) showed LOH on 8p, the majority of which (72%) had lost the entire short arm. Using 12 tumours with partial deletions of 8p, we have defined a minimum telomeric region of deletion between D8S264 and D8S133 (8p2l.1-pter). We also found LOH in the region 8pl1.2-12, where we have defined at least one centromeric target for deletion within a 4 cM interval. Two tumours were identified with loss of the telomeric region only, whereas all cases with loss in the centromeric region also had telomeric deletion. Chromosome 8p deletions have also been described in prostate, colorectal, hepatocellular, lung and endometrial carcinoma and collecting duct carcinoma of the kidney. It has been postulated that loss or inactivation of at least 2 tumour suppressor genes on 8p may play an important role in progression of both prostate and colorectal carcinomas. The regions of deletion we have identified in bladder tumours are compatible with these, suggesting that at least two genes on 8p may play a role in the development of many common solid tumours. Our findings significantly refine the localisation of the more centromeric of these loci.
Takle
L A
LA
Molecular Genetics Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey, UK.
Knowles
M A
MA
D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D004276:DNA, Satellite