GENETIC ALTERATIONS IN BLADDER-CANCER

To see whether genetic alterations follow a sequence of events leading to bladder cancer progression, 60 paired bladder tumours and normal t issues were analysed with polymorphic DNA markers, correlating loss of heterozygosity (LOH) at candidate tumour suppressor gene sites with p athological indices of poor clinical outcome. Distinct genotypic patte rns were associated with early and late stages of bladder cancer. 9q d eletions were observed in all superficial papillary tumours (Ta) and a lmost all tumours invading the lamina propria (T1), suggesting that th is event associates with the development of superficial bladder tumour s. However, 3p, 5q, and 17p deletions were absent in the Ta tumours bu t were identified in invasive bladder cancers. Two genetic pathways ch aracterise the evolution of superficial bladder tumours. 9qLOH was det ected in most Ta tumours, but in only 43% of muscle invasive neoplasms . Our hypothesis is that certain chromosomal abnormalities have a defi ned role in bladder tumour development, whereas others correlate with pathological indices of poor clinical outcome.