Identification of amplified and expressed genes in breast cancer by comparative hybridization onto microarrays of randomly selected cDNA clones
Identification of amplified and expressed genes in breast cancer by comparative hybridization onto microarrays of randomly selected cDNA clones
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DOI：
10.1002/gcc.10039
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发表时间：
2002-05-01
影响因子：
3.7
通讯作者：
Cooper, CS
中科院分区：
文献类型：
--
作者：
Clark, J;Edwards, S;Cooper, CS
利用已知人类基因集进行的微阵列分析为鉴定参与DNA扩增事件的候选癌基因提供了一个强大的平台，但存在一个缺点，即只能获取预先选择包含在阵列中的基因的信息。为了解决这个问题，我们对从一个cDNA文库中随机选取的克隆微阵列进行了比较基因组杂交（CGH）和表达分析，该cDNA文库是从含有正在研究的DNA扩增子的癌症中制备的。将这种方法应用于BT474乳腺癌细胞系（其在20q13、17q22 - 21和17q22 - 23处含有扩增子），鉴定出50个扩增且表达的基因，包括先前被提议为候选癌基因的来自这些区域的基因。当与微阵列表达谱和Northern分析的数据一起考虑时，我们能够提出5个基因作为新的候选癌基因，在乳腺癌细胞系中它们的扩增始终与较高水平的RNA表达相关。这些基因包括位于17q22 - 23的HB01组蛋白乙酰转移酶基因和位于17q11 - 21的TRAP100基因，TRAP100基因编码一种甲状腺激素受体相关蛋白共激活因子。结果证明了这种基于微阵列的CGH方法在寻找DNA扩增子内候选癌基因方面的实用性。（C）2002威利 - 利斯公司
Microarray analysis using sets of known human genes provides a powerful platform for identifying candidate oncogenes involved in DNA amplification events but suffers from the disadvantage that information can be gained only on genes that have been preselected for inclusion on the array. To address this issue, we have performed comparative genome hybridization (CGH) and expression analyses on microarrays of clones, randomly selected from a cDNA library, prepared from a cancer containing the DNA amplicon under investigation. Application of this approach to the BT474 breast carcinoma cell line, which contains amplicons at 20q13, 17q22-21, and 17q22-23, identified 50 amplified and expressed genes, including genes from these regions previously proposed as candidate oncogenes. When considered together with data from microarray expression profiles and Northern analyses, we were able to propose five genes as new candidate oncogenes where amplification in breast cancer cell lines was consistently associated with higher levels of RNA expression. These included the HB01 histone acetyl transferase gene at 17q22-23 and the TRAP100 gene, which encodes a thyroid hormone receptor-associated protein coactivator, at 17q11-21. The results demonstrate the utility of this microarray-based CGH approach in hunting for candidate oncogenes within DNA amplicons. (C) 2002 Wiley-Liss, Inc.