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Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array–comparative genomic hybridization

      Abstract

      We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can be applied to adenocarcinomas of the distal esophagus and gastroesophageal junction alike.
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      References

        • Lambert R.
        • Hainaut P.
        The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer.
        Best Pract Res Clin Gastroenterol. 2007; 21: 921-945
        • Forman D.
        Oesophago-gastric adenocarcinoma—an epidemiological perspective (review).
        Aliment Pharmacol Ther. 2004; 20: 55-60
        • Kalish R.J.
        • Clancy P.E.
        • Orringer M.B.
        • Appelman H.D.
        Clinical, epidemiologic, and morphologic comparison between adenocarcinomas arising in Barrett's esophageal mucosa and in the gastric cardia.
        Gastroenterology. 1984; 86: 461-467
        • Ruol A.
        • Parenti A.
        • Zaninotto G.
        • Merigliano S.
        • Costantini M.
        • Cagol M.
        • Alfieri R.
        • Bonavina L.
        • Peracchia A.
        • Ancona E.
        Intestinal metaplasia is the probable common precursor of adenocarcinoma in barrett esophagus and adenocarcinoma of the gastric cardia.
        Cancer. 2000; 88: 2520-2528
        • Siewert J.R.
        • Stein H.J.
        Classification of adenocarcinoma of the oesophagogastric junction.
        Br J Surg. 1998; 85: 1457-1459
        • Riegman P.H.
        • Vissers K.J.
        • Alers J.C.
        • Geelen E.
        • Hop W.C.
        • Tilanus H.W.
        • et al.
        Genomic alterations in malignant transformation of Barrett's esophagus.
        Cancer Res. 2001; 61: 3164-3170
        • Wu T.T.
        • Watanabe T.
        • Heitmiller R.
        • Zahurak M.
        • Forastiere A.A.
        • Hamilton S.R.
        Genetic alterations in Barrett esophagus and adenocarcinomas of the esophagus and esophagogastric junction region.
        Am J Pathol. 1998; 153: 287-294
        • El-Rifai W.
        • Frierson Jr., H.F.
        • Moskaluk C.A.
        • Harper J.C.
        • Petroni G.R.
        • Bissonette E.A.
        • et al.
        Genetic differences between adenocarcinomas arising in Barrett's esophagus and gastric mucosa.
        Gastroenterology. 2001; 121: 592-598
        • van Dekken H.
        • Geelen E.
        • Dinjens W.N.
        • Wijnhoven B.P.
        • Tilanus H.W.
        • Tanke H.J.
        • et al.
        Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of 14Q31–32.1 discriminates between esophageal (Barrett's) and gastric cardia adenocarcinomas.
        Cancer Res. 1999; 59: 748-752
        • Menke-Pluymers M.B.
        • van Drunen E.
        • Vissers K.J.
        • Mulder A.H.
        • Tilanus H.W.
        • Hagemeijer A.
        Cytogenetic analysis of Barrett's mucosa and adenocarcinoma of the distal esophagus and cardia.
        Cancer Genet Cytogenet. 1996; 90: 109-117
        • Moskaluk C.A.
        • Hu J.
        • Perlman E.J.
        Comparative genomic hybridization of esophageal and gastroesophageal adenocarcinomas shows consensus areas of DNA gain and loss.
        Genes Chromosomes Cancer. 1998; 22: 305-311
        • Varis A.
        • Puolakkainen P.
        • Savolainen H.
        • Kokkola A.
        • Salo J.
        • Nieminen O.
        • et al.
        DNA copy number profiling in esophageal Barrett adenocarcinoma: comparison with gastric adenocarcinoma and esophageal squamous cell carcinoma.
        Cancer Genet Cytogenet. 2001; 127: 53-58
        • Jonsson G.
        • Staaf J.
        • Olsson E.
        • Heidenblad M.
        • Vallon-Christersson J.
        • Osoegawa K.
        • et al.
        High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization.
        Genes Chromosomes Cancer. 2007; 46: 543-558
        • Snijders A.M.
        • Nowak N.
        • Segraves R.
        • Blackwood S.
        • Brown N.
        • Conroy J.
        • et al.
        Assembly of microarrays for genome-wide measurement of DNA copy number.
        Nat Genet. 2001; 29: 263-264
        • Jonsson G.
        • Naylor T.L.
        • Vallon-Christersson J.
        • Staaf J.
        • Huang J.
        • Ward M.R.
        • et al.
        Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization.
        Cancer Res. 2005; 65: 7612-7621
        • Saal L.H.
        • Troein C.
        • Vallon-Christersson J.
        • Gruvberger S.
        • Borg A.
        • Peterson C.
        BioArray Software Environment (BASE): a platform for comprehensive management and analysis of microarray data.
        Genome Biol. 2002; 3 (SOFTWARE0003)
        • Yang Y.H.
        • Dudoit S.
        • Luu P.
        • Lin D.M.
        • Peng V.
        • Ngai J.
        • et al.
        Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation.
        Nucleic Acids Res. 2002; 30: e15
        • Fernebro J.
        • Francis P.
        • Eden P.
        • Borg A.
        • Panagopoulos I.
        • Mertens F.
        • et al.
        Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma.
        Int J Cancer. 2006; 118: 1165-1172
        • Tusher V.G.
        • Tibshirani R.
        • Chu G.
        Significance analysis of microarrays applied to the ionizing radiation response.
        Proc Natl Acad Sci USA. 2001; 98: 5116-5121
        • Saeed A.I.
        • Sharov V.
        • White J.
        • Li J.
        • Liang W.
        • Bhagabati N.
        • et al.
        TM4: a free, open-source system for microarray data management and analysis.
        Biotechniques. 2003; 34: 374-378
        • Aust D.E.
        • Muders M.
        • Kohler A.
        • Schmidt M.
        • Diebold J.
        • Muller C.
        • et al.
        Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH analysis.
        Scand J Gastroenterol. 2004; 39: 766-772
        • Isola J.J.
        • Kallioniemi O.P.
        • Chu L.W.
        • Fuqua S.A.
        • Hilsenbeck S.G.
        • Osborne C.K.
        • et al.
        Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer.
        Am J Pathol. 1995; 147: 905-911
        • Hibi K.
        • Nakamura H.
        • Hirai A.
        • Fujikake Y.
        • Kasai Y.
        • Akiyama S.
        • et al.
        Loss of H19 imprinting in esophageal cancer.
        Cancer Res. 1996; 56: 480-482
        • Hourihan R.N.
        • O'Sullivan G.C.
        • Morgan J.G.
        Transcriptional gene expression profiles of oesophageal adenocarcinoma and normal oesophageal tissues.
        Anticancer Res. 2003; 23: 161-165
        • Tselepis C.
        • Morris C.D.
        • Wakelin D.
        • Hardy R.
        • Perry I.
        • Luong Q.T.
        • et al.
        Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro.
        Gut. 2003; 52: 174-180
        • Hughes S.J.
        • Glover T.W.
        • Zhu X.X.
        • Kuick R.
        • Thoraval D.
        • Orringer M.B.
        • et al.
        A novel amplicon at 8p22–23 results in overexpression of cathepsin B in esophageal adenocarcinoma.
        Proc Natl Acad Sci USA. 1998; 95: 12410-12415
        • Mitas M.
        • Almeida J.S.
        • Mikhitarian K.
        • Gillanders W.E.
        • Lewin D.N.
        • Spyropoulos D.D.
        • et al.
        Accurate discrimination of Barrett's esophagus and esophageal adenocarcinoma using a quantitative three-tiered algorithm and multimarker real-time reverse transcription–PCR.
        Clin Cancer Res. 2005; 11: 2205-2214
        • Holcombe R.F.
        • Marsh J.L.
        • Waterman M.L.
        • Lin F.
        • Milovanovic T.
        • Truong T.
        Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.
        Mol Pathol. 2002; 55: 220-226
        • Mendrzyk F.
        • Radlwimmer B.
        • Joos S.
        • Kokocinski F.
        • Benner A.
        • Stange D.E.
        • et al.
        Genomic and protein expression profiling identifies CDK6 as novel independent prognostic marker in medulloblastoma.
        J Clin Oncol. 2005; 23: 8853-8862
        • van Dekken H.
        • van Marion R.
        • Vissers K.J.
        • Hop W.C.
        • Dinjens W.N.
        • Tilanus H.W.
        • et al.
        Molecular dissection of the chromosome band 7q21 amplicon in gastroesophageal junction adenocarcinomas identifies cyclin-dependent kinase 6 at both genomic and protein expression levels.
        Genes Chromosomes Cancer. 2008; 47: 649-656
        • al-Kasspooles M.
        • Moore J.H.
        • Orringer M.B.
        • Beer D.G.
        Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas.
        Int J Cancer. 1993; 54: 213-219
        • Miller C.T.
        • Moy J.R.
        • Lin L.
        • Schipper M.
        • Normolle D.
        • Brenner D.E.
        • et al.
        Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade dysplasia.
        Clin Cancer Res. 2003; 9: 4819-4825
        • Rygiel A.M.
        • Milano F.
        • Ten Kate F.J.
        • Schaap A.
        • Wang K.K.
        • Peppelenbosch M.P.
        • et al.
        Gains and amplifications of c-myc, EGFR, and 20.q13 loci in the no dysplasia–dysplasia–adenocarcinoma sequence of Barrett's esophagus.
        Cancer Epidemiol Biomarkers Prev. 2008; 17: 1380-1385
        • Wang K.L.
        • Wu T.T.
        • Choi I.S.
        • Wang H.
        • Resetkova E.
        • Correa A.M.
        • et al.
        Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome.
        Cancer. 2007; 109: 658-667