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复发性膀胱癌的分子克隆分析

Molecular clonal analysis of recurrent bladder cancer.

作者信息

Junker Kerstin, Wolf Michael, Schubert Jörg

机构信息

Department of Urology, Lessingstr. 1, D-07743 Jena, Germany.

出版信息

Oncol Rep. 2005 Aug;14(2):319-23.

Abstract

In order to select the optimum therapy for patients at risk of recurrent bladder cancer, it is necessary to know the pathway of recurrence development. However, the origin of recurrent bladder cancer is controversially discussed. Therefore, the aim of our study was to define the clonal origin of recurrent tumors of the bladder using molecular genetic markers. Thirty cases with recurrent bladder cancer (1-4 recurrences per case) were investigated by microsatellite analysis using 4 markers for chromosome 9. PCR was performed according to standard protocols followed by gel electrophoresis and automated analysis using an automated DNA-Sequencer (LI-QOR). In 25 of 30 cases, loss of heterozygosity (LOH) occurred in at least 1 tumor. Identical LOH was detected in 20 cases. In all these cases the same allele was affected. Different LOH patterns were found in 4 cases showing LOH in only 1 tumor and in 1 case with alterations of different markers. In 5 cases, no alterations were detected using these markers. Our results show that the majority of bladder cancer recurrences are characterized by monoclonal origin. These data indicate that recurrence is caused by cell dissemination from the original tumor. For that reason, an early instillation therapy should be performed after transurethral resection.

摘要

为了为复发性膀胱癌风险患者选择最佳治疗方法,有必要了解复发发展的途径。然而,复发性膀胱癌的起源存在争议。因此,我们研究的目的是使用分子遗传标记来确定膀胱复发性肿瘤的克隆起源。通过使用针对9号染色体的4个标记进行微卫星分析,对30例复发性膀胱癌患者(每例有1-4次复发)进行了研究。按照标准方案进行聚合酶链反应(PCR),随后进行凝胶电泳,并使用自动DNA测序仪(LI-QOR)进行自动分析。在30例患者中的25例中,至少有1个肿瘤发生了杂合性缺失(LOH)。在20例中检测到相同的LOH。在所有这些病例中,受影响的是相同的等位基因。在4例仅在1个肿瘤中显示LOH的病例和1例不同标记发生改变的病例中发现了不同的LOH模式。在5例中,使用这些标记未检测到改变。我们的结果表明,大多数膀胱癌复发的特征是单克隆起源。这些数据表明,复发是由原始肿瘤中的细胞播散引起的。因此,经尿道切除术后应尽早进行灌注治疗。

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