The prevalence of loss of heterozygosity in chromosome 3, including FHIT, in bladder cancer, using the fluorescent multiplex polymerase chain reaction

Objective To determine some of the genetic alterations involved in the path ogenesis and progression of transitional cell carcinoma of the bladder. Materials and methods In a population-based study, freshly frozen tissue wa s collected from all patients newly diagnosed with urinary bladder cancer i n the Stockholm region during 1995-1996. The prevalence of loss of heterozy gosity (LOH) was assessed at seven sites on chromosome 3, analysed in 151 p atients, using a fluorescent multiplex polymerase chain reaction based on D NA from the tumour and peripheral blood. Results LOH was detected in 12.1% (at 3q25-26.2) to 23.1% (at 3p11-12) of t he informative cases. Relatively frequent LOH was detected at 3p22-24.2 (21 .6%), at 3p14.2 within FHIT (21.5%), and at 3p11-12 (22.1%). Of 151 tumours , 72 (47.7%) showed LOH at one or more loci on chromosome 3. LOH on chromos ome 3 was weakly associated with tumour grade (P=0.095), but not with tumou r stage (P=0.701). However, when the frequency of LOH was analysed individu ally at: each site, the prevalence of LOH at 3p11-12 was closely correlated with higher tumour stage (P=0.011). Replication errors were detected in on ly four of 151 (2.6%) rumours. Conclusion These findings suggest: that the 3p11-12 locus may involve a put ative candidate tumour-suppressor gene which might be associated with bladd er tumour invasiveness. The FHIT gene locus showed a relatively high freque ncy of LOH even in Ta tumours.