1. ¹Institute of Pathology, University Hospital Freiburg, Freiburg, Germany
2. ²Institute of Pathology, Technical University of Munich, Munich, Germany
3. ³Institute of Physics, University of Freiburg, Freiburg, Germany
4. ⁴Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Institute of Pathology, Neuherberg, Germany

Correspondence: Professor M Werner, MD, PhD, Institute of Pathology, University Hospital Freiburg, Breisacher Strasse 115 A, Freiburg 79106, Germany. E-mail: direktion-pathologie@uniklinik-freiburg.de

⁵These two authors contributed equally to this work.

Received 2 April 2008; Revised 13 May 2008; Accepted 14 May 2008; Published online 28 July 2008.

Abstract

We performed genome-wide analysis of copy-number changes and loss of heterozygosity (LOH) in Barrett's esophageal adenocarcinoma by single nucleotide polymorphism (SNP) microarrays to identify associated genomic alterations. DNA from 27 esophageal adenocarcinomas and 14 matching normal tissues was subjected to SNP microarrays. The data were analyzed using dChipSNP software. Copy-number changes occurring in at least 25% of the cases and LOH occurring in at least 19% were regarded as relevant changes. As a validation, fluorescence in situ hybridization (FISH) of 8q24.21 (CMYC) and 8p23.1 (SOX7) was performed. Previously described genomic alterations in esophageal adenocarcinomas could be confirmed by SNP microarrays, such as amplification on 8q (CMYC, confirmed by FISH) and 20q13 or deletion/LOH on 3p (FHIT) and 9p (CDKN2A). Moreover, frequent gains were detected on 2p23.3, 7q11.22, 13q31.1, 14q32.31, 17q23.2 and 20q13.2 harboring several novel candidate genes. The highest copy numbers were seen on 8p23.1, the location of SOX7, which could be demonstrated to be involved in amplification by FISH. A nuclear overexpression of the transcription factor SOX7 could be detected by immunohistochemistry in two amplified tumors. Copy-number losses were seen on 18q21.32 and 20p11.21, harboring interesting candidate genes, such as CDH20 and CST4. Finally, a novel LOH region could be identified on 6p in at least 19% of the cases. In conclusion, SNP microarrays are a valuable tool to detect DNA copy-number changes and LOH at a high resolution. Using this technique, we identified several novel genes and DNA regions associated with esophageal adenocarcinoma.