Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines
Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines
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DOI：
10.1002/gcc.20216
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发表时间：
2005-09-01
影响因子：
3.7
通讯作者：
McMahon, M
中科院分区：
文献类型：
--
作者：
Gysin, S;Rickert, P;McMahon, M
影响肿瘤抑制因子或癌基因（如KRAS 2、CDKN 2A、TP 53和DPC 4）表达和/或活性的基因组改变直接涉及人胰腺癌的发生和进展。为了进一步系统地表征这种疾病中发生的基因组改变，我们使用基于阵列的比较基因组杂交（CGH）对基因拷贝数的改变进行了全基因组分析。对于该分析，我们利用了一组25个人胰腺癌细胞系，这些细胞系来源于原发性或转移性肿瘤。该组还包括来源于科洛357细胞的细胞系的转移进展系列。阵列CGH允许识别可能参与胰腺癌细胞异常行为的基因拷贝数的改变。此外，通过科洛357细胞衍生物获得侵袭和转移潜力伴随着额外的局灶性基因组改变，包括KRAS 2的点突变和扩增。为了补充阵列CGH分析，我们还使用cDNA微阵列对这些细胞的一个子集中的mRNA表达模式进行了分析。通过这种方法，我们确定了一组候选基因，包括那些受RAS信号调节的基因，这些基因可能有助于癌细胞侵袭和转移的过程。本文的补充材料可以在基因、染色体和癌症网站http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html上找到。(c)2005 Wiley-Liss，Inc.
Genomic alterations influencing the expression and/or activity of tumor suppressors or oncogenes such as KRAS2, CDKN2A, TP53, and DPC4 have been directly implicated in the initiation and progression of human pancreatic adenocarcinoma. In an effort further to systematically characterize the genomic alterations that occur in this disease, we conducted a genome wide analysis of alterations in gene copy number using array-based comparative genomic hybridization (CGH). For this analysis, we utilized a panel of 25 human pancreatic cancer cell lines derived from either primary or metastatic tumors. This panel also included a metastatic progression series of cell lines derived from COLO 357 cells. Array CGH permitted the identification of alterations in the copy number of genes that might participate in the aberrant behavior of pancreatic cancer cells. In addition, the acquisition of invasive and metastatic potential by derivatives of COLO 357 cells was accompanied by additional focal genomic alterations including point mutations and amplification of KRAS2. To complement the array CGH analysis, we also conducted an analysis of mRNA expression patterns in a subset of these cells using cDNA microarrays. By this means, we identified a set of candidate genes, including those regulated by RAS signaling, that may contribute to the process of cancer cell invasion and metastasis. Supplementary material for this article can be found on the Genes, Chromosomes, and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html. (c) 2005 Wiley-Liss, Inc.