Genome-wide array-based comparative genomic hybridization reveals multiple amplification targets and novel homozygous deletions in pancreatic carcinoma cell lines
Genome-wide array-based comparative genomic hybridization reveals multiple amplification targets and novel homozygous deletions in pancreatic carcinoma cell lines
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DOI：
10.1158/0008-5472.can-03-3159
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发表时间：
2004-05-01
期刊：
影响因子：
11.2
通讯作者：
Höglund, M
中科院分区：
文献类型：
--
作者：
Heidenblad, M;Schoenmakers, EFPM;Höglund, M
胰腺癌表现出高度复杂的染色体异常，包括许多结构和数值畸变。有充分的证据表明，其中一些异常，例如反复扩增和纯合缺失，通过改变关键癌基因和抑癌基因的表达水平而促进肿瘤发生。为了加深对胰腺癌基因拷贝数变化的了解并确定关键的扩增/缺失靶标，我们对 31 种胰腺癌细胞系应用了基于全基因组阵列的比较基因组杂交。使用两种不同的微阵列，一种包含 3,565 个荧光原位杂交验证的细菌人工染色体克隆，另一种包含代表 17,494 个 UniGene 簇的 25,468 个 cDNA 克隆。总体而言，分析揭示了基因组的高度复杂性，在每种情况下都检测到了几个拷贝数变化。具体而言，鉴定了 32 个不同位置的 60 个扩增子，最常位于 8q（8 例）、12p（7 例）、7q（5 例）、18q（5 例）、19q（5 例）、6p（4 例）和 8p（4 例）内。 8q和12p的扩增分别主要集中在8q23-24和12p11-12，而其他染色体臂上的扩增则更加分散。此外，我们的分析还发现了位于 9p24、9p21、9q32、10p12、10q22、12q24 和 18q23 的几个新的纯合删除片段。不同病例的个体复杂性和畸变模式差异很大，即一些细胞系主要以高水平扩增为特征，而其他细胞系主要表现出全臂不平衡和纯合缺失。所描述的扩增和缺失靶标可能包含在胰腺肿瘤发生中重要的基因。
Pancreatic carcinomas display highly complex chromosomal abnormalities, including many structural and numerical aberrations. There is ample evidence indicating that some of these abnormalities, such as recurrent amplifications and homozygous deletions, contribute to tumorigenesis by altering expression levels of critical oncogenes and tumor suppressor genes. To increase the understanding of gene copy number changes in pancreatic carcinomas and to identify key amplification/deletion targets, we applied genome-wide array-based comparative genomic hybridization to 31 pancreatic carcinoma cell lines. Two different microarrays were used, one containing 3,565 fluorescence in situ hybridization-verified bacterial artificial chromosome clones and one containing 25,468 cDNA clones representing 17,494 UniGene clusters. Overall, the analyses revealed a high genomic complexity, with several copy number changes detected in each case. Specifically, 60 amplicons at 32 different locations were identified, most frequently located within 8q (8 cases), 12p (7 cases), 7q (5 cases), 18q (5 cases), 19q (5 cases), 6p (4 cases), and 8p (4 cases). Amplifications of 8q and 12p were mainly clustered at 8q23-24 and 12p11-12, respectively, whereas amplifications on other chromosome arms were more dispersed. Furthermore, our analyses identified several novel homozygously deleted segments located to 9p24, 9p21, 9q32, 10p12, 10q22, 12q24, and 18q23. The individual complexity and aberration patterns varied substantially among cases, i.e., some cell lines were characterized mainly by high-level amplifications, whereas others showed primarily whole-arm imbalances and homozygous deletions. The described amplification and deletion targets are likely to contain genes important in pancreatic tumorigenesis.