Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3
Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3
复制标题
DOI：
10.1038/sj.bjc.6602834
复制
发表时间：
2005-11-14
影响因子：
8.8
通讯作者：
Houlston, RS
中科院分区：
文献类型：
--
作者：
Hughes, S;Damato, BE;Houlston, RS
定义基因组不平衡区域可以识别参与肿瘤发展的基因。传统的细胞遗传学已经确定了葡萄膜黑色素瘤（UVM）中的几种非随机拷贝数改变（CNA），包括3号单体、6号染色体异常和8 q增加。为了进一步深入了解CNA和更精确地定义所涉及的区域，我们使用1 Mb BAC微阵列比较基因组杂交（CGH）分析了18个原发性UVM。我们的分析表明，最常见的基因组不平衡是8 q增益（78%），6p增益（67%）和单体3（56%）。两个不同的CGH配置文件可以划定的基础上的3号染色体的状态。在我们的研究中，单体3肿瘤中最常见的遗传变化是8q11.21-q24.3，6p25.1-p21.2，21q21.2-q21.3和21q22.13-q22.3的增加和1p36.33-p34.3，1p31.1-p21.2，6q16.2-q25.3和8p23.3-p11.23的丢失。相比之下，二体性3肿瘤仅显示6p25.3-p22.3和8q23.2-q24.3的复发性增益。我们的方法允许定义的最小重叠区域的不平衡，这可能是重要的UVM的发展。
Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21-q24.3, 6p25.1-p21.2, 21q21.2-q21.3 and 21q22.13-q22.3 and loss of 1p36.33-p34.3, 1p31.1-p21.2, 6q16.2-q25.3 and 8p23.3-p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3-p22.3 and 8q23.2-q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM.