The chromosome 9q genes TGFBR1, TSC1, and ZNF189 are rarely mutated in bladder cancer

This study assessed a series of bladder tumours and bladder tumour cell lin es for sequence variation in the Kruppel-like zinc finger gene ZNF189, the tuberous sclerosis complex gene 1 (TSC1), and the TGF beta receptor type I (TGFBR1), All three genes have been mapped to 9q regions commonly deleted i n transitional cell carcinoma of the bladder, Mutation analysis of the codi ng sequence of these genes revealed several variant bands that were shown t o represent polymorphisms. Mutation analysis of the ZNF189 gene in bladder cancer cell lines identified one amino acid substitution (lysine-->isoleuci ne) at position 323 in exon 4. For the TSC1 gene, two mutations were identi fied in two out of 27 independent cell lines. Both mutations result in a tr uncated protein. Furthermore, one out of 36 bladder tumours had a frameshif t mutation in exon 7 of the TSC1 gene. No tumour-specific mutations were fo und in the TGFBR1 gene. The length of the polyalanine tract present in exon 1 of the TGFBR1 gene was also investigated. It has been suggested that the allele with six alanines (6A) is more frequent in patients with bladder an d other cancers, so bladder cancer patients were compared with normal contr ols, In both groups, the percentage of heterozygotes was 17%. These data do not support a role for the 6A allele in bladder cancer susceptibility. Cop yright (C) 2001 John Wiley & Sons, Ltd.