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Infrequent somatic mutation of the MTS1 gene in primary bladder carcinomas
1Department of Biochemistry, Cancer Institute, Tokyo.
Abstract:
We examined a candidate tumor suppressor gene on chromosome 9p21, MTS1/CDK4I (multiple tumor suppressor 1/cyclin-dependent kinase 4 inhibitor), which has been found to be mutated frequently in cell lines derived from bladder carcinomas, for somatic mutations in 39 primary bladder cancers by means of SSCP (single-stranded conformational polymorphism) and DNA sequencing. Mutations were detected in two of these carcinomas; one was a 61-base deletion and the other a 1-base deletion. In both cases the homologous allele was missing, indicating that "two-hit" mutation of the MTS1 gene had taken place in these tumors. The results indicated that inactivation of the MTS1 gene is likely to be a contributing factor in some, but not the majority of, bladder cancers.
Insights
The MTS1/CDK4I gene, a potential tumor suppressor, was studied in bladder cancers. Mutations were found in two primary tumors, suggesting MTS1 gene inactivation contributes to some bladder cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The MTS1/CDK4I gene is a candidate tumor suppressor located on chromosome 9p21.
- Frequent mutations in MTS1/CDK4I have been observed in bladder carcinoma cell lines.
Purpose of the Study:
- To investigate somatic mutations in the MTS1/CDK4I gene in primary bladder cancers.
- To determine the role of MTS1/CDK4I gene inactivation in bladder tumorigenesis.
Main Methods:
- Analysis of 39 primary bladder cancers.
- Utilized single-stranded conformational polymorphism (SSCP) and DNA sequencing to detect mutations.
- Examined for "two-hit" mutations involving the homologous allele.
Main Results:
- Somatic mutations were identified in two of the 39 primary bladder cancers.
- The detected mutations included a 61-base deletion and a 1-base deletion.
- Loss of the homologous allele was observed in both cases, indicating "two-hit" inactivation.
Conclusions:
- Inactivation of the MTS1 gene is a contributing factor in a subset of bladder cancers.
- MTS1/CDK4I mutations do not appear to be a major cause of the majority of bladder cancers.