Homozygous deletions of p16(INK4) occur frequently in bilharziasis-associated bladder cancer.
We have studied p16(INK4) mutation (by PCR-SSCP) and deletion (by Southern blotting and/or multiplex PCR) in a series of 47 bilharziasis-associated tumors from Egypt and compared the results with those obtained on a series of 17 established bladder cell lines and non-bilharziasis-associated bladder cancers from the Netherlands. In the cell lines we found 9 homozygous deletions and 1 mutation (59% of p16(INK4) alterations in cell lines), whereas in cases from the Netherlands deletions were found in 4 of 22 samples. No mutations were detected in the 46 samples screened. Interestingly, in bilharziasis-associated bladder cancer, deletions were present in 23 samples and mutations in a further 2 cases (53% of p16(INK4) alteration in bilharziasis-associated bladder cancer). No correlation was found between p16(INK4) alteration and histopathological data. Likewise, the same frequency of alteration was found in tumors with different differentiation patterns (squamous, transitional or adenocarcinoma). Three conclusions can be drawn from our findings: (i) p16(INK4) alterations are more frequent in cell lines than in primary tumors; (ii) in primary bladder tumors (bilharziasis-associated or not), p16(INK4) deletions are much more frequent than p16(INK4) mutations; (iii) p16(INK4) alterations are more frequent in bilharziasis-associated bladder tumors than in other bladder tumors. This high frequency of deletion is not related to a specific histological type but to the specific etiology of these tumors.
Tamimi
Y
Y
Department of Urology/Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Bringuier
P P
PP
Smit
F
F
van Bokhoven
A
A
Abbas
A
A
Debruyne
F M
FM
Schalken
J A
JA
D002352:Carrier Proteins / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004534:Egypt; D017353:Gene Deletion; D006801:Humans; D009426:Netherlands; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012552:Schistosomiasis / Q000150:complications*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000469:parasitology
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16