title: The chromosome 9q genes TGFBR1, TSC1, and ZNF189 are rarely mutated in bladder cancer.
abstract: This study assessed a series of bladder tumours and bladder tumour cell lines for sequence variation in the Krüppel-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 in transitional cell carcinoma of the bladder. Mutation analysis of the coding sequence of these genes revealed several variant bands that were shown to represent polymorphisms. Mutation analysis of the ZNF189 gene in bladder cancer cell lines identified one amino acid substitution (lysine-->isoleucine) at position 323 in exon 4. For the TSC1 gene, two mutations were identified in two out of 27 independent cell lines. Both mutations result in a truncated protein. Furthermore, one out of 36 bladder tumours had a frameshift mutation in exon 7 of the TSC1 gene. No tumour-specific mutations were found 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 and other cancers, so bladder cancer patients were compared with normal controls. In both groups, the percentage of heterozygotes was 17%. These data do not support a role for the 6A allele in bladder cancer susceptibility.
authors.affiliation: Josephine Nefkens Institute, Department of Pathology, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: A A
authors.initials: AA
authors.lastname: van Tilborg
authors.forename: A
authors.initials: A
authors.lastname: de Vries
authors.forename: E C
authors.initials: EC
authors.lastname: Zwarthoff
mesh_terms: D030201:Activin Receptors, Type I; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D018125:Receptors, Transforming Growth Factor beta; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C114474:ZNF189 protein, human; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human