p53 mutations in human bladder cancer.
Environ Mol Mutagen
; 24(3): 156-60, 1994.
Article
in En
| MEDLINE
| ID: mdl-7957118
ABSTRACT
Mutations in the tumor suppressor gene p53 play an important role in carcinogenesis and tumor progression. To assess the status of p53 from genomic DNA from bladder cancer samples a two stage polymerase chain reaction was employed. The technique provided material for subsequent detection of mutations by Single Strand Conformation Polymorphism (SSCP) analysis followed by DNA sequence analysis. SSCP analysis of exons 5 to 9 of p53 was performed using fragments from PCR end-labeled with 32P followed by autoradiography using an electrophoresis system with temperature control. This SSCP method improved resolution of mutations in exons 5, 7, and 8 and the sharpness of bands in exons 6 and 9. Bands with altered migration patterns were excised from the dried SSCP gels, reamplified by PCR, and sequenced. Mutations in conserved exons 5, 6, 7, 8, and 9 of the p53 gene were analyzed from bladder tumor biopsies. Our results are consistent with the literature in that mutations in p53 are predominantly found in high grade bladder cancer (Odds Ratio = 4.05, Fisher Exact P = 0.104); however, the results were not statistically significant due to small numbers. Eight of 35 (23%) tumor samples examined showed mutations in p53 (including two double mutations). Six of 13 (46%) grade III and IV tumors had p53 mutations vs. 2 of 17 (12%) grade I and II tumors. Normal individuals carried no p53 mutations. We found no correlation between pack years of smoking and mutation in p53. The spectrum of mutations confirmed a high proportion of GC CG transversions as well as the occurrence of double mutations.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder Neoplasms
/
Carcinoma in Situ
/
Carcinoma, Transitional Cell
/
Genes, p53
/
Mutation
Limits:
Humans
/
Male
Language:
En
Journal:
Environ Mol Mutagen
Journal subject:
BIOLOGIA MOLECULAR
/
SAUDE AMBIENTAL
Year:
1994
Type:
Article
Affiliation country:
Canada