Genomic characterization of esophageal squamous cell carcinoma from a high-risk population in China.
Genomic characterization of esophageal squamous cell carcinoma from a high-risk population in China.
复制标题
DOI：
10.1158/0008-5472.can-08-4622
复制
发表时间：
2009-07-15
期刊：
影响因子：
11.2
通讯作者：
Lee MP
中科院分区：
文献类型：
--
作者：
Hu N;Wang C;Ng D;Clifford R;Yang HH;Tang ZZ;Wang QH;Han XY;Giffen C;Goldstein AM;Taylor PR;Lee MP
基因组不稳定性在大多数人类癌症中起着重要作用。为了表征食管鳞状细胞癌（ESCC）的基因组不稳定性，我们使用Affymetrix基因芯片人类图谱500K （n=30例）和人类U133A （n=17例）阵列检测了中国高风险地区食管鳞状细胞癌（ESCC）患者的杂合性缺失（LOH）、拷贝数缺失（CN）、拷贝数增加（CN）和基因表达。我们发现不同病例的基因组不稳定性测量差异很大，并将其分为两组：高频不稳定性组（三分之二的病例有一个或多个不稳定性类别≥10%）和低频不稳定性组（三分之一的病例不稳定性< 10%）。基因组不稳定性在染色体臂之间也有很大差异，9p上的LOH频率最高（33%的信息性单核苷酸多态性（snp））， 3p上的CN丢失（33%）和3q上的CN获得（48%）。鉴定出22个LOH区域：4个在9p上，7个在9q上，4个在13q上，2个在17p上，5个在17q上。检测到三个CN损失区- 3p12.3, 4p15.1和9p21.3。共发现12个CN增益区，其中3q有6个，7q有1个，8q有4个，11q有1个。这些CN增益区中基因最丰富的一个是11q13.1-13.4，其中26个基因也有RNA表达数据。超过80%的这些基因的RNA表达增加与CN增加显著相关。我们的研究结果表明，将CN分析和基因表达数据结合起来鉴定参与食管癌发生的基因具有潜在的实用性。
Genomic instability plays an important role in most human cancers. To characterize genomic instability in esophageal squamous cell carcinoma (ESCC), we examined loss of heterozygosity (LOH), copy number (CN) loss, CN gain, and gene expression using the Affymetrix GeneChip Human Mapping 500K (n=30 cases) and Human U133A (n=17 cases) arrays in ESCC cases from a high-risk region of China. We found that genomic instability measures varied widely among cases and separated them into two groups: a high-frequency instability group (two-thirds of all cases with one or more instability category ≥ 10%) and a low-frequency instability group (one-third of cases with instability < 10%). Genomic instability also varied widely across chromosomal arms, with the highest frequency of LOH on 9p (33% of informative single nucleotide polymorphisms (SNPs)), CN loss on 3p (33%), and CN gain on 3q (48%). Twenty-two LOH regions were identified: four on 9p, seven on 9q, four on 13q, two on 17p, and five on 17q. Three CN loss regions – 3p12.3, 4p15.1, and 9p21.3 – were detected. Twelve CN gain regions were found, including six on 3q, one on 7q, four on 8q, and one on 11q. One of the most gene-rich of these CN gain regions was 11q13.1-13.4, where 26 genes also had RNA expression data available. CN gain was significantly correlated with increased RNA expression in over 80% of these genes. Our findings demonstrate the potential utility of combining CN analysis and gene expression data to identify genes involved in esophageal carcinogenesis.