Analysis of p21(WAF1/CIP1) in primary bladder tumors Journal Article
| Authors: | Lacombe, L.; Orlow, I.; Silver, D.; Gerald, W. L.; Fair, W. R.; Reuter, V. E.; Cordon-Cardo, C. |
| Article Title: | Analysis of p21(WAF1/CIP1) in primary bladder tumors |
| Abstract: | The p21(WAF1/CIP1) gene is regulated by p53 and encodes a cyclin- dependent kinase (Cdk)-inhibitor involved in senescence and cell quiescence. The role of p21 as a negative regulator of cell proliferation suggests that it may function as a tumor suppressor gene. However, only a few mutations of the p21(WAF1/CIP1) gene have been reported to date. In order to assess potential p21(WAF1/CIP1) gene alterations in human bladder cancer, we have examined this gene and its encoded product in a well-characterized cohort of 27 primary bladder tumors. Mobility shifts by single-strand conformation polymorphism in the p21(WAF1/CIP1) gene were identified in 2 cases. Sequencing analyses revealed that one of these cases had point mutations in the 3' untranslated region, while the other case had a frame shift mutation at positions 322 (C to A) and a deletion of 8 nucleotides (323→331; CCG→ACG, codon 81 Arg→Thr) that produced a stop signal at codon 83 (Gly→Stop). This tumor had a p21-negative phenotype by immunohistochemistry, but did not lose any allele. We further characterized these cases by the study of TP53 mutations using single-strand conformation polymorphism (PCR- SSCP) and sequencing, as well as immunohistochemical assays. Seven mobility shifts were identified and seven cases showed p53 nuclear accumulation. The two cases displaying mutated p21(WAF1/CIP1) had wild-type TP53. It is concluded that p21(WAF1/CIP1) gene aberrations are infrequent in bladder carcinoma but may be occasionally identified in primary bladder tumors. |
| Keywords: | adult; clinical article; human tissue; aged; aged, 80 and over; middle aged; gene mutation; gene sequence; genetics; mutation; polymerase chain reaction; metabolism; cell cycle; pathology; bladder cancer; bladder tumor; urinary bladder neoplasms; physiology; cancer genetics; oncogene; tumor suppressor gene; biosynthesis; dna; dna, neoplasm; urinary bladder; cyclin dependent kinase inhibitor 1a; cyclin-dependent kinase inhibitor p21; cycline; carcinoma, transitional cell; cyclins; transitional cell carcinoma; genes, tumor suppressor; cdkn1a protein, human; p21(waf1/cip1); single strand conformation polymorphism; humans; human; male; female; priority journal; article |
| Journal Title: | Oncology Research |
| Volume: | 8 |
| Issue: | 10-11 |
| ISSN: | 0965-0407 |
| Publisher: | Cognizant Communication Corporation |
| Date Published: | 1996-01-01 |
| Start Page: | 409 |
| End Page: | 414 |
| Language: | English |
| PUBMED: | 9114433 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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