Mutation of the 9q34 gene TSC1 in sporadic bladder cancer

Deletions involving chromosome 9 occur in more than 50% of human bladder ca ncers of all grades and stages. Most involve loss of the whole chromosome o r of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor gene s. We have localized such a critical region of deletion at 9q34 between the markers D9S149 and D9S66, an interval which contains the Tuberous Sclerosi s gene TSC1. Single strand conformation polymorphism (SSCP) and sequence an alysis of TSC1 in bladder tumours and cell lines with 9q34 loss of heterozy gosity (LOH) has identified five mutations in retained TSC1 alleles. Our re sults support the hypothesis that TSC1 can act as a bladder tumour suppress or gene.