High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH
High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH
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DOI：
10.1002/ijc.21491
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发表时间：
2006-03-15
影响因子：
6.4
通讯作者：
Lam, WL
中科院分区：
文献类型：
--
作者：
Garnis, C;Lockwood, WW;Lam, WL
含有肿瘤抑制基因和癌基因的染色体区域经常被缺失或扩增。阵列比较基因组杂交检测肿瘤DNA相对于正常对照的节段性DNA拷贝数变化。细菌人工染色体阵列最近的发展，以一种平铺路径的方式跨越了人类基因组，有32,000个克隆，促进了以前所未有的分辨率进行全基因组图谱分析。利用这一技术，我们全面描述和比较了28个常用的非小细胞肺癌(NSCLC)细胞模型的基因组，这些细胞模型来自18例腺癌(AC)、9例鳞癌和I例大细胞癌。在这种分辨率下的分析不仅为这些模型细胞系中的每一个提供了详细的基因组改变模板，而且揭示了频繁复制和缺失的新区域。值得注意的是，对7号染色体的详细分析确定了该染色体上6个不同的变化区域，暗示该染色体上存在多个新的癌基因位点。此外，鳞状细胞和AC细胞之间的比较发现，这两种亚型都有共同的变化，例如3P的丢失和5P的增加，此外还有更频繁地与I亚型相关的多个热点。有趣的是，已知在两种亚型中都被扩增的染色体3Q显示了两个不同的改变区域，I在鳞状细胞中经常改变，I在AC中更频繁地改变。总之，我们的数据显示了通过对非小细胞肺癌基因组的高分辨率分析产生的独特信息，并揭示了在不同的非小细胞肺癌亚型中普遍存在的遗传改变。(C)2005年Wiley-Liss，Inc.
Chromosomal regions harboring tumor suppressors and oncogenes are often deleted or amplified. Array comparative genomic hybridization detects segmental DNA copy number alterations in tumor DNA relative to a normal control. The recent development of a bacterial artificial chromosome array, which spans the human genome in a tiling path manner with > 32,000 clones, has facilitated whole genome profiling at an unprecedented resolution. Using this technology, we comprehensively describe and compare the genomes of 28 commonly used non-small cell lung carcinoma (NSCLC) cell models, derived from 18 adenocarcinomas (AC), 9 squamous cell carcinomas and I large cell carcinoma. Analysis at such resolution not only provided a detailed genomic alteration template for each of these model cell lines, but revealed novel regions of frequent duplication and deletion. Significantly, a detailed analysis of chromosome 7 identified 6 distinct regions of alterations across this chromosome, implicating the presence of multiple novel oncogene loci on this chromosome. As well, a comparison between the squamous and AC cells revealed alterations common to both subtypes, such as the loss of 3p and gain of 5p, in addition to multiple hotspots more frequently associated with only I subtype. Interestingly, chromosome 3q, which is known to be amplified in both subtypes, showed 2 distinct regions of alteration, I frequently altered in squamous and I more frequently altered in AC. In summary, our data demonstrate the unique information generated by high resolution analysis of NSCLC genomes and uncover the presence of genetic alterations prevalent in the different NSCLC subtypes. (c) 2005 Wiley-Liss, Inc.