Multifocal transitional cell carcinoma of the bladder and upper urinary tract: Molecular screening of clonal origin by characterizing CD44 alternative splicing patterns
Multifocal transitional cell carcinoma of the bladder and upper urinary tract: Molecular screening of clonal origin by characterizing CD44 alternative splicing patterns
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DOI：
10.1097/01.ju.0000129541.23460.48
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发表时间：
2004-09-01
影响因子：
6.6
通讯作者：
Eto, H
中科院分区：
文献类型：
--
作者：
Miyake, H;Hara, I;Eto, H
目的：CD 44是一种广泛表达的细胞表面粘附分子，在癌症发生过程中，其各种异构体由选择性RNA剪接机制产生。我们评估是否多灶性移行细胞癌的尿路上皮是由于外地的变化和/或腔内播种和implantation.Materials和方法：在一系列的24例同步和/或异时性多发性尿路上皮癌，我们进行了逆转录聚合酶链反应分析，使用一组引物能够扩增所有的CD 44剪接变异体亚型。在聚合酶链反应产物被重新测定后，对与主要同种型（即CD 44 s、CD 44 v10和CD 44 v8 -10）对应的带强度和面积进行定量，并计算CD 44 v10与CD 44 s和CD 44 v8 -10与CD 44 s的比率。结果：24例膀胱癌中18例CD 44-V10/CD 44 s和CD 44-V8 - 10/CD 44 s的比值在多发性尿路上皮癌中无显著性差异。然而，在其余6例病例中，这些比率在多个癌症病变中差异很大。此外，不同类型的p53突变中检测到的多发性癌病变中只有2例，这也表明不同的模式的CD 44选择性splicing.Conclusions：这些发现表明，至少有一些多发性移行细胞癌的尿路上皮。基于对CD 44的选择性RNA剪接的分析，似乎是独立的来源。p53基因突变的检测进一步证实了这一假说。
Purpose: CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism during cancer initiation. We assessed whether multifocal transitional cell carcinoma of the urothelium is due to field change and/or intraluminal seeding and implantation.Materials and Methods: In a series of 24 patients with synchronous and/or metachronous multiple urothelial cancers we performed reverse transcription-polymerase chain reaction analysis using a set of primers capable of amplifying all CD44 splice variant isoforms. After polymerase chain reaction products were electrophoresed band intensities with areas corresponding to the major isoforms (that is CD44s, CD44v10 and CD44v8-10) were quantified, and CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios were calculated. Moreover, p53 gene mutations in exons 4 to 11 were screened by direct DNA sequencing.Results: Of these 24 cases 18 showed similar CD44v10-to-CD44s and CD44-V 8 -10-to-CD44s ratios in among multiple urothelial cancers in each case. However, in the remaining 6 cases these ratios were quite different among multiple cancer lesions. Furthermore, different types of p53 mutation were detected among multiple cancer lesions in only 2 of 24 cases, which also indicated different patterns of CD44 alternative splicing.Conclusions: These findings suggest that at least some multiple transitional cell carcinomas of the urothelium. seem to be of independent origin based on the analysis of alternative RNA splicing of CD44. Moreover, this hypothesis was further supported by the evaluation of p53 gene mutation.