Bladder neoplasms--regions at chromosome 9 with putative tumour suppressor genes.
OBJECTIVE
To investigate the prevalence of loss of heterozygosity (LOH) at 12 different loci on chromosome 9 in patients with bladder neoplasms using a newly developed fluorescent multiplex polymerase chain reaction.


METHODS
In a population-based study, freshly frozen tissue was collected from all cases of newly detected bladder neoplasms in the Stockholm region during 1995 and 1996 (n = 538) and 156 representative cases were subsequently studied in the present series.


RESULTS
In total, at one or more loci of chromosome 9, 89% (139/156) of the tumours showed LOH. Loss of heterozygosity in informative cases was in the range from 33.1% (41/124) at the 9p21 locus to 67% (77/115) at the 9q31.3-32 loci. When minor LOH was studied, representing a single LOH with retention of heterozygosity at both adjacent markers, relatively frequent losses were detected at 9q22.3 harbouring the PTCH gene (7.7%), at 9q32-33.1 (6.6%) and at 9q33.2 harbouring the DBCCR1 gene (7.5%). In relation to clinical information, LOH at 9p22.1 was statistically significantly correlated with tumour grade (p = 0.01), but not with tumour stage. Replication errors were observed in 14 of 156 (9%) tumours.


CONCLUSIONS
Our observation of relatively frequent minor LOH at 9p22.1, 9q22.3 and 9q32-33.1 identifies regions within which putative tumour suppressor genes, including the PTCH and the DBCCR1 genes, may reside.
Department of Biosciences at Novum, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Takashi
T
Wada
Petra
P
Berggren
Gunnar
G
Steineck
Jan
J
Adolfsson
Hans
H
Wijkström
Ulf
U
Norming
Johan
J
Hansson
Kari
K
Hemminki
Per
P
Larsson
D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology