Related Experiment Videos
Identification of p53 gene mutations in bladder cancers and urine samples
D Sidransky1, A Von Eschenbach, Y C Tsai
1Department of Oncology, Johns Hopkins University, Baltimore, MD 21231.
Abstract:
Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene products. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.
Insights
Genetic alterations in the p53 suppressor gene are common in invasive bladder cancers. Detecting these p53 mutations in urine sediment offers potential for early cancer monitoring.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer is a prevalent malignancy with poorly understood molecular origins.
- The p53 tumor suppressor gene plays a critical role in cellular regulation and is frequently implicated in cancer development.
Purpose of the Study:
- To investigate the frequency and nature of p53 gene mutations in primary invasive bladder cancers.
- To explore the potential of detecting p53 mutations in non-invasive samples like urine for clinical applications.
Main Methods:
- Analysis of p53 gene alterations in 18 invasive bladder tumor samples.
- Utilizing polymerase chain reaction (PCR) and oligomer-specific hybridization to detect p53 mutations in urine sediment.
Main Results:
- Sixty-one percent (11 out of 18) of bladder tumors exhibited p53 genetic alterations, including point mutations and deletions.
- p53 mutations were detected in 1-7% of cells in the urine sediment of three patients.
- Mutations often co-occurred with chromosome 17p allelic deletions, suggesting loss of functional p53.
Conclusions:
- p53 gene mutations are a frequent early event in the pathogenesis of invasive bladder cancer.
- Ex vivo detection of p53 mutations in urine sediment presents a promising avenue for non-invasive bladder cancer monitoring.