HOMOZYGOUS DELETIONS OF P16(INK4) OCCUR FREQUENTLY IN BILHARZIASIS-ASSOCIATED BLADDER-CANCER

We have studied p16(INK4) mutation (by PCR-SSCP) and deletion (by Sout hern blotting and/or multiplex PCR) in a series of 47 bilharziasis-ass ociated 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) alterat ions in cell lines), whereas in cases from the Netherlands deletions w ere found in 4 of 22 samples. No mutations were detected in the 46 sam ples screened. Interestingly, in bilharziasis-associated bladder cance r, deletions were present in 23 samples and mutations in a further 2 E ases (53% of p16(INK4) alteration in bilharziasis-associated bladder c ancer). No correlation was found between p16(INK4) alteration and hist opathological data. Likewise, the same frequency of alteration was fou nd in tumors with different differentiation patterns (squamous, transi tional or adenocarcinoma). Three conclusions can be drawn from our fin dings: (i) p16(INK4) alterations are more frequent in cell lines than in primary tumors; (ii) in primary bladder tumors (bilharziasis-associ ated or not), p16(INK4) deletions are much more frequent than p16(INK4 ) mutations; (iii) p16(INK4) alterations are more frequent in bilharzi asis-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. (C) 1996 Wiley-Liss, Inc .