Definition of two regions of deletion on chromosome 9 in carcinoma of the bladder.

Loss of heterozygosity (LOH) at loci on chromosome 9 can be detected in more than 50% of bladder tumours, suggesting the presence on this chromosome of one or more suppressor genes for bladder carcinogenesis. Localisation of the target gene(s) by deletion mapping has previously proved difficult due to the uneven distribution of polymorphic loci and the finding of LOH at all these loci in the majority of tumours. We have used a panel of 22 highly informative microsatellite markers, evenly distributed along chromosome 9 to analyse LOH in 95 cases of primary transitional cell carcinoma of the bladder. Forty nine tumours (53%) showed LOH at one or more loci. Of these, 30 had LOH at all informative loci, indicating probable monosomy 9. Nineteen tumours (22%) had subchromosomal deletions, 5 of 9p only, 9 of 9q only and 5 of both 9p and 9q with a clear region of retention of heterozygosity between. The patterns of LOH in these tumours indicated a common region of deletion on 9p between D9S126 (9p21) and IFNA (9p21). A single tumour showed a second site of deletion on 9p telomeric to IFNA indicating the possible existence of 2 target genes on 9p. All deletions of 9q were large, with a common region of deletion between D9S15 (9q13-q21.1) and D9S60 (9q33-q34.1). These results indicate a much higher frequency of subchromosomal deletion than has previously been detected and provide evidence for the simultaneous involvement of distinct suppressor loci on 9p and 9q in bladder carcinoma.