GENETIC-STUDIES AND MOLECULAR MARKERS OF BLADDER-CANCER

Target genes implicated in cellular transformation and tumor progressi on have been divided into two categories: proto-oncogenes which, when activated, become dominant events characterized by the gain of functio n, and tumor suppressor genes which become recessive events characteri zed by the loss of function. Alterations in proto-oncogenes and tumor suppressor genes seem equally prevalent among human cancers. Multiple mutations appear to be required to conform the malignant phenotype. Pr oto-oncogenes are activated mainly by point mutations; however, amplif ication and translocation events are also common. Tumor suppressor gen es are inactivated by an allelic loss followed by a point mutation of the remaining allele. The prototype suppressor genes are the retinobla stoma (RE) gene and the TP53 (also known as p53) genes. Recent studies have shown that inactivation of TP53 and RE occur in bladder tumors t hat have a more aggressive clinical outcome and poor prognosis. We wil l review the molecular abnormalities associated with both oncogenes an d tumor suppressor genes in bladder tumors, and also discuss the poten tial clinical use of their detection. The implementation of objective predictive assays to identify these alterations in clinical material w ill enhance our ability to assess tumor biological activities and to d esign effective treatment regimes. (C) 1997 Wiley-Liss, Inc.