MOLECULAR ALTERATIONS IN BLADDER-CANCER

In recent years, significant information has been accumulated on the m olecular alterations that take place during development of transitiona l cell carcinoma (TCC). A number of studies aimed at defining loss of heterozygosity have shown a general chromosomal instability in TCC wit h loss of parts of chromosome 9 at early stages of papillomas, and of chromosomes 11, 13, 3, 4, 8, 17 and 18 during further development of t he tumor. Oncogenes are activated, exemplified by mutations in the ras gene family and overexpression of the c-erbB-2 gene, in a minor fract ion of tumors. Alterations of tumor suppressors (involved in control o f the cell cycle, DNA quality control and activation of apoptosis) see m to be frequently involved. Among these p53 has a key role, and one p 53 allele is frequently lost in TCC followed by mutation of the remain ing allele. These alterations are correlated with survival, disease pr ogression, invasion and recurrence. Also frequently lost are the cell cycle control genes p16 and p15. The predictive value of this has not yet been determined. Studies of glycosylation genes have shown downreg ulation of the ABO gene, followed by loss of ABO blood group structure s and accumulation of the Lewis cell adhesion molecules in high grade tumors. Functional proteome analysis has furthermore identified biomar kers that are correlated with grade and stage. Molecular models for TC C development can now be built, and clinical testing of these is urgen tly needed.