Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis
Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis
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DOI：
10.1016/j.lungcan.2007.08.037
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发表时间：
2008-03-01
期刊：
影响因子：
5.3
通讯作者：
Hawthorn, Lesleyann
中科院分区：
文献类型：
--
作者：
Lo, Ken C.;Stein, Leighton C.;Hawthorn, Lesleyann
肺癌是世界上癌症死亡的主要原因，鳞状细胞癌（SqCC）是该组中第二常见的癌症。基因组DNA拷贝数改变是SqCC以及其他上皮来源的癌症的发展和进展中的基本遗传事件。鉴定肿瘤抑制基因（TSG）和在肿瘤起始和进展期间受影响的癌基因的能力可以促进鉴定用于治疗干预的新型分子靶点并提供诊断生物标志物。尽管肺癌中的许多基因改变的关联，肿瘤进展的分子机制仍然是模糊的，因为通常太多的候选人被发现使用传统的基因微阵列分析。为了克服这种模仿，我们已经在SqCC中鉴定了在相同肿瘤中显示出一致的基因表达变化的基因，所述基因表达变化使用微阵列分析与通过BAC阵列比较基因组杂交（aCGH）定义的DNA拷贝数改变来定义。使用内部重叠算法同步两次分析所得数据。虽然与正常对照相比，许多基因的表达水平发生了变化，但与拷贝数变化相关的基因要少得多，为生物学研究提供了可管理的数量。我们鉴定了2000多个基因，这些基因表现出基因表达改变，并映射到表现出相应损失或获得的BAC。进一步严格的统计分析确定了损失或增益的最小重叠区域，其显示映射到这些区域的基因表达的同时减少或增加。一致的增益涉及3q 23-q29，5p15.1-q11.1和染色体18和20，而一致的损失涉及3p26.3-p12.3，9p24.3-q34.3和染色体17和19。这两种方法之间的一致性发现表明，DNA拷贝数的改变可以直接影响基因表达模式，从而影响肺部SqCC中的肿瘤发生。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Lung cancer is the leading cause of cancer deaths in the world and squamous cell carcinoma (SqCC) is the second most common in this group. Genomic DNA copy number alterations are fundamental genetic events in the development and progression of SqCC as well as other epithelial-derived cancers. The ability to identify tumor suppressor genes (TSGs) and oncogenes that are affected during tumor initiation and progression could facilitate the identification of novel molecular targets for therapeutic intervention and provide diagnostic biomarkers. Despite the association of many genetic alterations in lung cancer the molecular mechanisms of tumor progression remain ambiguous since often too many candidates are revealed using conventional genetic microarray analysis. To overcome this (imitation, we have identified genes in SqCC which show concordant gene expression changes defined using microarray analysis with DNA copy number alterations defined by BAC-array comparative genomic hybridization (aCGH) in the same tumors. An in-house overlay algorithm was used to synchronize the data resulting from the two analyses. Although the expression Levels of many genes were altered when compared to normal controls, those which correlated with copy number changes were far fewer, providing a manageable number for biological studies. We identified over 2000 genes which displayed both gene expression alterations and mapped to BACs which demonstrated a corresponding loss or gain. A further stringent statistical analysis identified minimal regions of overlap for losses or gains which displayed a coincident decrease or increase in the expression of genes mapping to those regions. Consistent gains involved 3q23-q29, 5p15.1-q11.1 and chromosomes 18 and 20, while consistent losses involved 3p26.3-p12.3, 9p24.3-q34.3, and chromosomes 17 and 19. The concordance finding between these two approaches suggests that DNA copy number alterations can directly influence gene expression patterns that impact on tumorigenesis in SqCC of the lung. (C) 2007 Elsevier Ireland Ltd. All rights reserved.