Genome-wide detection of chromosomal imbalances in tumors using BAC microarrays
Genome-wide detection of chromosomal imbalances in tumors using BAC microarrays
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DOI：
10.1038/nbt0402-393
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发表时间：
2002-04-01
影响因子：
46.9
通讯作者：
Bradley, A
中科院分区：
文献类型：
--
作者：
Cai, WW;Mao, JH;Bradley, A
染色体不平衡，如缺失和扩增是大多数肿瘤中常见的重排（1）。特异性重排始终与特定肿瘤类型或阶段相关，暗示了染色体不平衡区域中的基因在肿瘤发生和进展中的作用（2）。比较基因组杂交（CGH）（3）的发展消除了从肿瘤中获得中期扩散的需要，因此可以使用提取的基因组DNA样本揭示许多实体瘤中的染色体不平衡。然而，细胞遗传学方法的分辨率仍然存在，并且CGH的极端技术难度限制了其使用。从概念上讲，基于DNA微阵列的计算全息图是解决传统计算全息图所有局限性的一个明显方案。尽管阵列已用于CGH研究（5-8），但其成功受到特定信噪比差的限制。在这里，我们展示了一种基于微阵列的CGH方法，可以可靠地检测染色体缺失和高分辨率扩增。我们的微阵列系统是从根本上不同于目前大多数微阵列技术，激活的DNA是打印在天然玻璃表面，而其他系统几乎完全专注于激活的表面，一个策略，总是引入杂交背景。使用预改性的概念通常可以应用于制造其他生物材料的阵列，因为改性基底在溶液中比在表面上更可控。
Chromosomal imbalances such as deletions and amplifications are common rearrangements in most tumors(1). Specific rearrangements are consistently associated with specific tumor types or stages, implicating the role of the genes in a region of chromosomal imbalance in tumor initiation and progression(2). The development of comparative genomic hybridization (CGH)(3) has obviated the need to obtain metaphase spreads from tumors, so that the chromosomal imbalances in many solid tumors may be revealed using an extracted genomic DNA sample. However, the resolution of the cytogenetic method remains and the extreme technical difficulty of CGH has restricted its use. Conceptually, DNA microarray(4)-based CGH is an obvious solution to all of the limitations of conventional CGH. Although arrays have been used for CGH studies(5-8), their success has been limited by poor specific signal-to-noise ratios. Here we demonstrate a microarray-based CGH method that allows reliable detection of chromosomal deletions and amplifications with high resolution. Our microarray system is fundamentally different from most current microarray technologies in that activated DNA is printed on natural glass surfaces while other systems almost exclusively focus on activating the surfaces, a strategy that invariably introduces hybridization backgrounds. The concept of using pre-modification may be generally applied for making arrays of other biological materials, as modifying the substrates will be more controllable in solution than on surfaces.