Genetic alterations as clonal markers for bladder cancer detection in urine

Bladder cancer is the result of a clonal expansion of cancer cells in which multiple genetic alterations have accumulated. Point mutations of the p53 gene are frequently observed in bladder cancer. Loss of a retinoblastoma (Rb) allele is also common in bladder cancer. Recent data have shown frequent loss of heterozygosity (LOH) and homozygous deletion of 9p21, including the region of p16INK4A, a putative tumor suppressor gene, in bladder cancer. LOH is also observed frequently at several other chromosome regions in bladder cancer. These genetic changes have proved useful as clonal markers in the detection of cancer cells in urine. Because of their complexity, most molecular diagnostic approaches are not considered promising cancer screening tools in patients or high-risk populations. However, a new molecular approach, the examination of microsatellite alterations in bladder cancer and urine specimens, is a promising screening tool for the disease. The common genetic alterations in bladder cancer and their use as clonal markers in screening or diagnosis strategies will be discussed.