High-resolution characterization of the pancreatic adenocarcinoma genome
High-resolution characterization of the pancreatic adenocarcinoma genome
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DOI：
10.1073/pnas.0402932101
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发表时间：
2004-06-15
影响因子：
11.1
通讯作者：
Chin, L
中科院分区：
文献类型：
--
作者：
Aguirre, AJ;Brennan, C;Chin, L
胰腺癌基因组含有多个扩增和缺失，表明存在许多致癌基因和肿瘤抑制基因，驱动这种致命癌症的发生和发展。在这里，阵列比较基因组杂交的cDNA微阵列平台和信息学工具已被用来定义在一组24胰腺癌细胞系和13个原发性肿瘤标本的拷贝数改变。这种高分辨率的基因组分析已经确定了所有已知的区域性增益和损失，以及许多以前未表征的高度复发的拷贝数改变。一个系统的优先顺序方案选择了64个焦点最小共同区域（MCR）的经常性拷贝数变化。这些MCR的平均大小为2.7 Mb，其中21个（33%）MCR的跨度为1 Mb或更小（中位数为0.33 Mb），平均拥有15个注释基因。此外，对这64个优先MCR内的显著部分基因的互补表达谱分析使得能够鉴定基因剂量和mRNA表达之间具有统计学显著关联的候选者子集。因此，DNA和RNA谱的整合为发现参与胰腺癌发病机制的基因提供了一个高产的切入点。
The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes and tumor suppressor genes driving the genesis and progression of this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma.