Short communicationArray comparative genomic hybridization, expression array, and protein analysis of critical regions on chromosome arms 1q, 7q, and 8p in adenocarcinomas of the gastroesophageal junction
Introduction
Adenocarcinomas in Barrett's esophagus are generally in an advanced stage at the time of detection, and the reported overall 5-year survival rates are only 10-20% [1], [2]. Reflux disease has been suggested to be the most important etiological factor in the development of gastroesophageal junction adenocarcinomas. In the esophagus, long-standing reflux disease can result in Barrett's esophagus, in which squamous cell epithelium has undergone metaplastic change to columnar epithelium. Barrett's esophagus is associated with a highly increased risk of developing adenocarcinoma [3]. Metaplastic change has also been observed at the gastroesophageal junction and in the gastric cardia [4], [5].
Gastroesophageal junction adenocarcinomas have been characterized in several genome-wide comparative genomic hybridization studies. Gains were detected most frequently at 1q, 3q, 6p, 7p, 7q, 8q, 17q, and 20q; recurrent losses were found at 4p, 4q, 5q, 8p, 9p, 17p, and 18q [6], [7], [8], [9], [10], [11], [12], [13] Gene amplification in esophageal adenocarcinomas has been investigated by molecular methods [14]. The gene most commonly amplified was ERBB2, on chromosome 17q12. Next are a number of other genes, including MET, EGFR, and MYC. Comparative genomic hybridization (CGH) with a commercial DNA array comprising 287 cancer-related DNA targets showed frequent amplification of several genes [15].
Recently, we reported that gain of 1q32 and loss of 8p22 are associated with progressive cancer behavior (i.e., recurrence-free period or lymphatic dissemination) in early stage esophageal adenocarcinomas [16] and we reported the frequent amplification of 7q21 in gastroesophageal junction cancers [17]. The genes underlying these aberrant regions, however, had not been detected. Our objective, therefore, was to identify these critically altered genes using straightforward and robust approaches.
Section snippets
Tumor samples
The study material comprised 11 fresh-frozen tumor specimens (from 10 men and 1 woman; mean age, 63.2 years): 8 Barrett-related adenocarcinomas of the esophagus and 3 cancers of the proximal stomach cancers (gastric cardia). In addition, cell lines OE19, OE33, M5.1, and SKGT-4 were investigated. Three of these cell lines were derived from esophageal adenocarcinomas and one from and gastric cardia. Barrett-related adenocarcinomas were clearly located in the distal esophagus in the presence of
Results and discussion
We performed genomic and expression analyses of critical chromosomal regions on 15 selected gastroesophageal junction adenocarcinomas: 11 primary adenocarcinomas and 4 cell lines. Eleven of these cancers were esophageal (Barrett-related), 4 originated from the gastric cardia. The primary adenocarcinomas comprised 3 TNM stage I, 4 stage II, 2 stage III and 2 stage IV tumors. We applied array comparative genomic hybridization (aCGH) and mRNA expression analysis using a custom-made fine-tiling
Acknowledgments
This work was supported by the Dutch Cancer Society (grant DDHK 2002-2700).
References (26)
Barrett's esophagus, dysplasia and adenocarcinoma
Hum Pathol
(1994)- et al.
Prevalence of metaplasia at the gastro-esophageal junction
Lancet
(1994) - et al.
Molecular cytogenetic evaluation of gastric cardia adenocarcinoma and precursor lesions
Am J Pathol
(2001) - et al.
Spectrum of genetic changes in gastro-esophageal cancer cell lines determined by an integrated molecular cytogenetic approach
Cancer Genet Cytogenet
(2002) - et al.
Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence
Am J Pathol
(2000) - et al.
Genomic array and expression analysis of frequent high-level amplifications in adenocarcinomas of the gastro-esophageal junction
Cancer Genet Cytogenet
(2006) - et al.
Engineering zinc finger protein transcription factors: the therapeutic relevance of switching endogenous gene expression on or off at command
J Mol Biol
(2005) - et al.
Rising incidence of adenocarcinoma of the esophagus and gastric cardia
JAMA
(1991) - et al.
Increased incidence of adenocarcinomas at the gastro-oesophageal junction in Dutch males since the 1990s
Eur J Gastroenterol Hepatol
(2002) - et al.
Intestinal metaplasia of the gastric cardia
Am J Gastroenterol
(1997)
Consistent genetic alterations in xenografts of proximal stomach and gastro-esophageal junction adenocarcinomas
Cancer Res
Comparative genomic hybridization of esophageal and gastroesophageal adenocarcinomas shows consensus areas of DNA gain and loss
Genes Chromosomes Cancer
Comparative genomic hybridization of cancer of the gastro-esophageal junction: deletion of 14q31-32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas
Cancer Res
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Current address: Department of Pathology, Sint Lucas Andreas Hospital, P.O. Box 9243, 1006 AE Amsterdam, The Netherlands.