Tamimi Y, Bringuier P P, Smit F, van Bokhoven A, Abbas A, Debruyne F M, Schalken J A
Department of Urology/Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Int J Cancer. 1996 Oct 9;68(2):183-7. doi: 10.1002/(SICI)1097-0215(19961009)68:2<183::AID-IJC7>3.0.CO;2-U.
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.
我们通过聚合酶链反应-单链构象多态性分析（PCR-SSCP）研究了47例来自埃及的血吸虫病相关肿瘤中p16（INK4）基因的突变情况，并通过Southern印迹法和/或多重PCR研究了该基因的缺失情况。我们将研究结果与17株已建立的膀胱癌细胞系以及来自荷兰的非血吸虫病相关膀胱癌的研究结果进行了比较。在细胞系中，我们发现了9例纯合缺失和1例突变（细胞系中p16（INK4）改变的发生率为59%），而在来自荷兰的病例中，22个样本中有4个检测到缺失。在筛查的46个样本中未检测到突变。有趣的是，在血吸虫病相关膀胱癌中，23个样本存在缺失，另有2例存在突变（血吸虫病相关膀胱癌中p16（INK4）改变的发生率为53%）。p16（INK4）改变与组织病理学数据之间未发现相关性。同样，在不同分化模式（鳞状、移行或腺癌）的肿瘤中，p16（INK4）改变的频率相同。从我们的研究结果可以得出三个结论：（i）p16（INK4）改变在细胞系中比在原发性肿瘤中更常见；（ii）在原发性膀胱肿瘤（无论是否与血吸虫病相关）中，p16（INK4）缺失比p16（INK4）突变更常见；（iii）p16（INK4）改变在血吸虫病相关膀胱肿瘤中比在其他膀胱肿瘤中更常见。这种高缺失频率与特定的组织学类型无关，而是与这些肿瘤的特定病因有关。
