CONCOMITANT GASTRIN AND ERBB2 GENE AMPLIFICATIONS AT 7Q12-Q21 IN THE INTESTINAL-TYPE OF GASTRIC-CANCER

Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12-q21 region is very common in the i ntestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)-specific and ERBB2-specifi c probes on ten specimens of gastric carcinoma that, by using comparat ive genomic hybridization, showed I) DNA copy number gain or amplifica tion at 17q12-q21,a region known to harbor the GAS and ERBB2 genes (fo ur cases); 2) gain of the entire chromosome 17 (three cases); or 3) no rmal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric canter cell lines with or without gain at 17q12-q21 as well as a breast cance r cell line with ERBB2 amplification. Our results showed that simultan eous amplification of both GAS and ERBB2 was four- to ninefold in the tumors with the 17q12-q21 amplification. Both genes were amplified in the same nuclei, and the hybridization signals were localized to the s ame region of the nucleus. Overexpression of GAS and ERBB2 was observe d by Western immunoblotting only in the gastric cancer cell line with gain at 17q12-q21. The ERBB2 amplification is also a recurrent change in breast cancer. To investigate whether the GAS amplification is uniq ue in gastric cancer, Fluorescence in situ hybridization analysis was performed on 40 breast cancer cell lines. The ERBB2 amplification was observed in 11 cell lines, but none of the lines showed the GAS amplif ication. This indicates that the formation of an amplicon, in which bo th the GAS and the ERBB2 genes are amplified, might be unique in gastr ic cancer, especially in its intestinal type, and that simultaneous am plification of both genes is important to the tumorigenesis of intesti nal gastric cancer. We demonstrate here for the first time that a gene of a physiological hormone is amplified in tumors that originate from cells that normally secrete the hormone. Genes Chromosomes Cancer 24: 24-29, 1999. (C) 1999 Wiley-Liss, Inc.