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Decreased expression of the p16/MTS1 gene without mutation is frequent in human urinary bladder carcinomas
M Asamoto1, Y Iwahori, T Okamura
1Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Abstract:
The p16 (CDKN2,MTS1) gene is located at 9p21 and its product, p16, inhibits the cyclin D/CDK4 complex. Loss of heterozygosity on chromosome 9p is very common in human bladder carcinomas and has been found in all stages of lesions, suggesting that it occurs early in bladder tumor progression. Several studies have revealed frequent homozygous deletion of the p16 gene in cell lines, and that such deletions are also common in some types of cancers. In addition, point mutations in the p16 gene have been identified in several types of neoplasia. In the present examination of urinary bladder tumors, no p16 gene mutations were detected, but nine cases out of 23 (39%) showed decreased mRNA expression, revealed by the reverse transcriptase polymerase chain reaction. There were no histological differences apparent between those cases with normal and those with decreased p16 expression. These results indicate that while p16 gene mutations may be rare, changes in the level of the p16 transcripts could play a role in human bladder carcinoma development.
Insights
Decreased p16 mRNA expression, not mutations, was observed in 39% of bladder carcinomas. This suggests altered p16 transcript levels may contribute to bladder cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p16 gene (CDKN2, MTS1) at 9p21 encodes a protein inhibiting the cyclin D/CDK4 complex.
- Loss of heterozygosity on chromosome 9p is common in bladder carcinomas, indicating early involvement in tumor progression.
- Previous studies noted frequent homozygous deletions and point mutations of the p16 gene in various cancers.
Purpose of the Study:
- To investigate the role of the p16 gene in human urinary bladder tumors.
- To determine the frequency of p16 gene mutations and alterations in mRNA expression in bladder cancer.
Main Methods:
- Analysis of p16 gene mutations in urinary bladder tumors.
- Assessment of p16 mRNA expression levels using reverse transcriptase polymerase chain reaction (RT-PCR).
Main Results:
- No p16 gene mutations were detected in the examined bladder tumors.
- Decreased p16 mRNA expression was found in 9 out of 23 cases (39%).
- No significant histological differences were observed between tumors with normal and decreased p16 expression.
Conclusions:
- While p16 gene mutations appear infrequent in bladder carcinoma, alterations in p16 transcript levels may play a role in its development.
- Reduced p16 mRNA expression is a potential mechanism contributing to human bladder cancer progression.