P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

Abstract:

:Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

LaRue H,Allard P,Simoneau M,Normand C,Pfister C,Moore L,Meyer F,Têtu B,Fradet Y

doi

10.1093/carcin/21.1.101

keywords:

subject

Has Abstract

pub_date

2000-01-01 00:00:00

pages

101-6

issue

1

eissn

0143-3334

issn

1460-2180

journal_volume

21

pub_type

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