The bladder cancer genome; chromosomal changes as prognostic makers, opportunities, and obstacles.

During the past decades, the complexity of the bladder cancer genome has become evident. Early cytogenetic studies identified several patterns of chromosomal changes, particularly the frequent loss of chromosome 9. The cytogenetic approach was replaced by molecular methods, such as comparative genome hybridization (CGH) and loss of heterozygosity (LOH) analyses that describe genomic changes at a molecular and higher resolution. With these methods, the full complexity of the bladder cancer genome has been better appreciated. Using CGH and LOH analyses, it also became apparent that premalignant lesions of the bladder, such as hyperplasia and dysplasia, as well as carcinoma in situ (CIS), showed genomic changes. Whole genome analyses showed that low stage, low grade tumors generally show fewer changes than tumors of higher stage and grade. In addition, several genomic alterations were shown to be highly specific for more aggressive and invasive tumors. Based on the general association between complex genomic changes and tumor behavior, several investigations have been directed towards the identification of prognostic genomic markers for urothelial cancer. A complicating factor in the analysis and understanding of bladder cancer genomic progression is that recurring and, hence, chronologically later tumors may show genomes less rearranged than preceding tumors. Furthermore, morphologically normal urothelium in patients with bladder cancer frequently show the same type of genomic alterations as the tumor proper. This makes an issue of to what extent information on genomic changes will produce reliable prognostic information when limited to the tumor proper