This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-4622v1 69/14/5908    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hu, N. Articles by Lee, M. P. PubMed PubMed Citation Articles by Hu, N. Articles by Lee, M. P.

Genomic Characterization of Esophageal Squamous Cell Carcinoma from a High-Risk Population in China

¹ Division of Cancer Epidemiology and Genetics and ² Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ³ Shanxi Cancer Hospital, Taiyuan, Shanxi, PR China; and ⁴ Information Management Service, Inc., Silver Spring, Maryland

Requests for reprints: Philip R. Taylor, Genetic Epidemiology Branch, DCEG, National Cancer Institute, EPS, Room 7006, MSC 7236, Bethesda, MD 20892-7236. Phone: 301-594-2932; Fax: 301-402-4489; E-mail: ptaylor{at}mail.nih.gov or Maxwell P. Lee, Laboratory of Population Genetics, Building 41, Room D702, 41 Library Drive, Bethesda, MD 20892. Phone: 301-435-8956; Fax: 301-435-8963; E-mail: leemax{at}mail.nih.gov.

Key Words: esophageal cancer • LOH • copy number alteration • 500K SNP array

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 of 10%) and a low-frequency instability group (one-third of cases with instability of <10%). Genomic instability also varied widely across chromosomal arms, with the highest frequency of LOH on 9p (33% of informative single nucleotide polymorphisms), 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 show the potential utility of combining CN analysis and gene expression data to identify genes involved in esophageal carcinogenesis. [Cancer Res 2009;69(14):5908–17]