Initiation of bladder cancer may involve deletion of a tumour-suppressor gene on chromosome 9

Abstract

Although many genetic lesions including suppressor gene inactivation have been identified in sporadic tumours, the identity of the common initiating or early genetic events in most cases remains obscure. We have analysed tumour and leucocyte DNA from a series of 252 primary human bladder tumours of all grades and stages for deletions of chromosome 9. Probes from four polymorphic loci were used to detect loss of heterozygosity (LOH) in tumour specimens. Fifty-nine per cent of tumours from patients informative at one or more of these loci showed LOH. A comparison of LOH for markers on 9p and 9q indicated that proximal 9p or 9q is the likely site for a candidate bladder tumour-suppressor gene. Most strikingly, LOH was observed not only in tumours of high grade or stage but also in > 50% of grade 1 and 2 superficial (pTa) tumours. This is the first change to be identified at significant frequency in such tumours. Inactivation of a tumour-suppressor gene on chromosome 9 may therefore be an early genetic event in the development of bladder cancer.