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 tissues were analysed with polymorphic DNA markers, correlating loss of heterozygosity (LOH) at candidate tumour suppressor gene sites with pathological indices of poor clinical outcome. Distinct genotypic patterns were associated with early and late stages of bladder cancer. 9q deletions were observed in all superficial papillary tumours (Ta) and almost all tumours invading the lamina propria (T1), suggesting that this event associates with the development of superficial bladder tumours. However, 3p, 5q, and 17p deletions were absent in the Ta tumours but were identified in invasive bladder cancers. Two genetic pathways characterise the evolution of superficial bladder tumours. 9qLOH was detected in most Ta tumours, but in only 43% of muscle invasive neoplasms. Our hypothesis is that certain chromosomal abnormalities have a defined role in bladder tumour development, whereas others correlate with pathological indices of poor clinical outcome.