Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses
Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses
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DOI：
10.1038/sj.onc.1209690
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发表时间：
2006-11-01
期刊：
影响因子：
8
通讯作者：
Monni, O.
中科院分区：
文献类型：
--
作者：
Jarvinen, A-K;Autio, R.;Monni, O.
头颈部鳞状细胞癌发生和发展的分子机制仍知之甚少。已经描述了许多遗传改变，但在大多数情况下，这种改变的分子后果仍不清楚。在这里，我们进行了一个集成的高分辨率微阵列分析基因拷贝数和表达在20喉癌细胞系和原发性肿瘤。我们的目的是确定在疾病发病机制中起关键作用的遗传改变，并确定其表达直接受这些事件影响的基因。利用定制开发的生物信息学方法，实现了基于阵列的比较基因组杂交的DNA水平数据与来自寡核苷酸微阵列的RNA水平信息的整合。高水平扩增对基因表达有明显的影响。在整个基因组中，739个基因的过表达可归因于细胞系中的基因扩增事件，其中325个基因在原发性肿瘤中显示出相同的现象，包括11q13处的FADD和PPFIA1。基因本体和通路分布的分析进一步确定了可能识别治疗干预的潜在靶点的基因。我们的数据突出了可能对喉癌进展至关重要并提供潜在治疗靶点的基因。
Molecular mechanisms contributing to initiation and progression of head and neck squamous cell carcinoma are still poorly known. Numerous genetic alterations have been described, but molecular consequences of such alterations in most cases remain unclear. Here, we performed an integrated high-resolution microarray analysis of gene copy number and expression in 20 laryngeal cancer cell lines and primary tumors. Our aim was to identify genetic alterations that play a key role in disease pathogenesis and pinpoint genes whose expression is directly impacted by these events. Integration of DNA level data from array-based comparative genomic hybridization with RNA level information from oligonucleotide microarrays was achieved with custom-developed bioinformatic methods. High-level amplifications had a clear impact on gene expression. Across the genome, overexpression of 739 genes could be attributed to gene amplification events in cell lines, with 325 genes showing the same phenomenon in primary tumors including FADD and PPFIA1 at 11q13. The analysis of gene ontology and pathway distributions further pinpointed genes that may identify potential targets of therapeutic intervention. Our data highlight genes that may be critically important to laryngeal cancer progression and offer potential therapeutic targets.