Novel regions of chromosomal amplification at 6p21, 5p13, and 12q14 in gastric cancer identified by array comparative genomic hybridization

Gastric cancer (GC) frequently displays changes in DNA copy number, but few studies have precisely correlated specific genetic alterations with changes in gene expression. We undertook both array comparative genomic hybridization (aCGH) and expression analyses of 20 primary GCs using a cDNA microarray with more than 9,300 genes. Diverse clinical and histopathologic tumor subtypes, including signet-ring tumors and tumors at the gastroesophageal junction, were analyzed. All tumors showed changes in gene copy number, with the majority showing multiple changes. Regions of gain and loss were generally consistent with previous cytogenetic reports; however, the use of aCGH greatly increased the resolution of measured genomic change. By comparing gene expression and high-resolution measurement of gene copy number directly, we were able to identify several regions of high-level gain associated with substantially increased gene expression that have not been defined previously in GC. Novel candidate oncogenes included dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2) and protein tyrosine kinase 7 (PTK7). (C) 2004 Wiley-Liss, Inc.