Cancer Genetics and Cytogenetics 127 (2001) 53–58 0165-4608/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S0165-4608(00)00423-4 DNA copy number profiling in esophageal Barrett adenocarcinoma: comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma Asta Varis a , Pauli Puolakkainen b , Hanna Savolainen b , Arto Kokkola b , Jarmo Salo b , Outi Nieminen b , Stig Nordling c , Sakari Knuutila a, * a Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland b Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland c Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland Received 21 September 2000; accepted 2 November 2000 Abstract We screened 18 specimens of Barrett adenocarcinoma for genetic alterations using comparative genomic hybridization (CGH) to analyze DNA copy number changes. The most common gains were at 20q (56%) and 17q (39%). High-level amplifications were observed in the same chromo- somes. The most common losses were in chromosomes 4 (22%) and 5 (22%). Other recurrent changes were gains of chromosomes 8, 10q, and 13. We compared the copy number changes in Barrett adenocarcinoma and those previously reported in the intestinal type of stomach carci- noma. The similarities we found suggest a common molecular pathogenesis, whereas dissimilari- ties seen between Barrett adenocarcinoma and esophageal squamous cell carcinoma are in keep- ing with a well-known different etiology. © 2001 Elsevier Science Inc. All rights reserved. 1. Introduction Barrett esophagus is defined as a columnar epithelium-lined distal esophagus, in which the normal stratified squamous epi- thelium is replaced by metaplastic columnar epithelium con- taining goblet cells [1–5]. Barrett esophagus develops as a re- sult of chronic gastroesophageal reflux and it is associated with an increased risk of developing esophageal adenocarcinoma [1–5]. Dysplasia arises from the metaplastic epithelium and precedes adenocarcinoma in Barrett esophagus [5]. The risk of patients with Barrett esophagus to develop adenocarcinoma is 30- to 125-fold as compared with the general population [5]. Reports from the 1970s and 1980s have shown an increasing rate in the occurrence of esophageal adenocarcinoma and the trend has continued in the 1990s [6,7]. Cytogenetic data of Barrett adenocarcinoma are scanty. Studies using karyotyping and in situ hybridization have re- vealed frequent losses of chromosomes 4, 18, 21, and Y, gains in chromosomes 14 and 20, and aberrations at 1,3,11, and 22 [8,9]. Loss of heterozygosity (LOH) has been ob- served in tumor suppressor gene TP53 mapped to 17p13.1 [10–12]. In addition, allelic losses have been found at 18q and 5q [13,14]. Dolan et al. [14] detected LOH at the sites of tumor suppressor genes DCC, APC, and TP53. Elevated ex- pression of the cyclin-dependent kinase inhibitor p21 corre- lates with p53 expression [12]. Nakamura et al. [15] found overexpression of the ERBB2 oncoprotein by immunohis- tochemical staining in adenocarcinoma of Barrett esophagus. ERBB2 protein overexpression was detected in 57 of 80 tu- mors (71%) and it correlated significantly with the depth of tumor invasion, distant metastases, and tumor stage. The most significant findings in our previous study of the intestinal type of gastric cancer were 17q and 20q ampli- cons [16]. To investigate whether these findings are com- mon in Barrett carcinoma, we used comparative genomic hybridization (CGH) to analyze 18 specimens of Barrett ad- enocarcinoma for genetic imbalances. Furthermore, we compared our results with the CGH profiles of esophageal squamous cell carcinoma. 2. Materials and methods 2.1. Patients Archival paraffin-embedded specimens from 18 Barrett adenocarcinoma patients were obtained from the Depart- * Corresponding author. Tel.: + 358-9-1912-6527; fax: + 358-9-1912- 6788. E-mail address: sakari.knuutila@helsinki.fi (S. Knuutila).