The p21(WAF1/CIP1) gene is regulated by p53 and encodes a cyclin-depen
dent kinase (Cdk)-inhibitor involved in senescence and cell quiescence
. The role of p21 as a negative regulator of cell proliferation sugges
ts that it may function as a tumor suppressor gene. However, only a fe
w mutations of the p21(WAF1/CIP1) gene have been reported to date. In
order to assess potential p21(WAF1/CIP1) gene alterations in human bla
dder cancer, we have examined this gene and its encoded product in a w
ell-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 t
he 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 t
umor 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-SSC
P) and sequencing, as well as immunohistochemical assays. Seven mobili
ty shifts were identified and seven cases showed p53 nuclear accumulat
ion. The two cases displaying mutated p21(WAF1/CIP1) had wild-type TP5
3. It is concluded that p21(WAF1/CIP1) gene aberrations are infrequent
in bladder carcinoma but may be occasionally identified in primary bl
adder tumors. Copyright (C) 1996 Elsevier Science Inc.