Integrated Analysis of Genome-Wide DNA Copy Number and Gene Expression with Patient Outcomes in Esophageal Adenocarcinoma [Copy Number]

Esophageal adenocarcinoma (EAC) is now the most common esophageal malignancy in the United States with >15,000 new cases per year. Prognosis for patients with EAC is poor due to both late diagnosis and early metastasis to lymph nodes. The goal of this study was to perform an integrated analysis of genome-wide DNA copy number changes, gene expression and patient clinical data in order to identify events and genes associated with clinical endpoints or that may play a key role in EAC development and therefore provide potential therapeutic targets. Specifically, we report on a series of 116 EAC specimens studied using Affymetrix SNP 6.0 and U133 Plus 2 GeneChip arrays plus additional cohorts of 73 and 114 EAC patients whose tumors were analyzed using Affymetrix StyI 250K arrays and fluorescence in-situ hybridization (FISH) respectively. Integration of this genomic data with clinical information and outcomes enabled identification of copy number changes and coordinate gene expression events that are associated with patient prognosis, that validate known or suspected oncogenes and tumor suppressor genes and that also facilitate identification of novel, putative driver genes in large regions of copy number gain and loss. These findings add to our understanding of the basic biology of EAC and provide a guide for development of novel prognostic tools and therapies. Copy number analysis of Affymetrix 250K Sty (n=73) and SNP6.0 arrays (n=116) was performed for 189 esophageal adenocarcinoma samples. There are also 72 samples from normal squamous esophageal epithelium, which were used as references for copy number inference for the 250K Sty array data and 15 samples from white blood cells used as references for copy number inference for the SNP6.0 array data.