Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation
Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation
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DOI：
10.1038/sj.bjc.6603850
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发表时间：
2007-07-10
影响因子：
8.8
通讯作者：
Ogawa, O.
中科院分区：
文献类型：
--
作者：
Kawanishi, H.;Takahashi, T.;Ogawa, O.
这项研究的目的是通过基于阵列的比较基因组杂交(ARRAY-CGH)和FGFR突变分析，研究同一患者多灶性低级别浅表尿路上皮肿瘤异时性和/或同步发展过程中基因改变的累积。我们分析了5名患者的24个肿瘤(PTA-1、G1-2)。我们先前通过微卫星分析确定了每个患者肿瘤之间的克隆关系。这一次，无监督的分层聚类分析显示，来自每个患者的肿瘤被聚集在一起，而不是来自其他患者的肿瘤。所有来自同一患者的肿瘤都显示出2-7个相同的区域或整个手臂的染色体变化。此外，还发现了几个单独的变化。分支图显示，基因改变的累积不能用线性模型解释，并假设在四名患者中存在假设的前体细胞。在某些情况下，FGFR突变似乎发生在多灶性肿瘤发展的较晚阶段。综上所述，这些发现表明，低级别浅表性尿路上皮肿瘤在多灶性发展过程中积累了轻微的基因改变，尽管这些肿瘤在遗传上是稳定的。
The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low- grade superficial urothelial tumours in the same patient, by using array- based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2-7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable.