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Genetic studies and molecular markers of bladder cancer
C Cordon-Cardo1, J Sheinfeld, G Dalbagni
1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. cordon-c@mskcc.org
Abstract:
Target genes implicated in cellular transformation and tumor progression have been divided into two categories: proto-oncogenes which, when activated, become dominant events characterized by the gain of function, and tumor suppressor genes which become recessive events characterized 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. Proto-oncogenes are activated mainly by point mutations; however, amplification and translocation events are also common. Tumor suppressor genes are inactivated by an allelic loss followed by a point mutation of the remaining allele. The prototype suppressor genes are the retinoblastoma (RB) gene and the TP53 (also known as p53) genes. Recent studies have shown that inactivation of TP53 and RB occur in bladder tumors that have a more aggressive clinical outcome and poor prognosis. We will review the molecular abnormalities associated with both oncogenes and tumor suppressor genes in bladder tumors, and also discuss the potential clinical use of their detection. The implementation of objective predictive assays to identify these alterations in clinical material will enhance our ability to assess tumor biological activities and to design effective treatment regimes.
Insights
Proto-oncogenes and tumor suppressor genes drive cancer. In bladder tumors, TP53 and retinoblastoma (RB) gene inactivation correlate with aggressive disease, suggesting their detection can guide treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cellular transformation and tumor progression involve proto-oncogenes (gain-of-function) and tumor suppressor genes (loss-of-function).
- Alterations in these genes are prevalent in human cancers, with multiple mutations often required for malignancy.
- Proto-oncogenes activate via point mutations, amplification, or translocation; tumor suppressor genes inactivate through allelic loss and subsequent point mutation.
Purpose of the Study:
- To review molecular abnormalities of oncogenes and tumor suppressor genes in bladder tumors.
- To discuss the clinical utility of detecting these genetic alterations.
- To highlight the role of TP53 and retinoblastoma (RB) genes in bladder cancer prognosis.
Main Methods:
- Review of molecular abnormalities in oncogenes and tumor suppressor genes.
- Analysis of TP53 and RB gene inactivation in bladder tumors.
- Discussion of potential clinical applications of genetic marker detection.
Main Results:
- Inactivation of TP53 and RB genes is observed in bladder tumors.
- These inactivations are associated with a more aggressive clinical outcome and poorer prognosis.
- Proto-oncogene activation and tumor suppressor gene inactivation are key events in bladder cancer development.
Conclusions:
- TP53 and RB gene inactivation are significant indicators of aggressive bladder tumors.
- Detecting these molecular abnormalities can improve tumor assessment and treatment strategies.
- Objective predictive assays for genetic alterations will enhance clinical decision-making in bladder cancer.