title: Concomitant gastrin and ERBB2 gene amplifications at 17q12-q21 in the intestinal type of gastric cancer.
abstract: Our recent studies using comparative genomic hybridization showed that gain or amplification at the 17q12-q21 region is very common in the intestinal type of gastric cancer. Here, we describe a fluorescence in situ hybridization study with gastrin (GAS)-specific and ERBB2-specific probes on ten specimens of gastric carcinoma that, by using comparative genomic hybridization, showed 1) DNA copy number gain or amplification at 17q12-q21, a region known to harbor the GAS and ERBB2 genes (four cases); 2) gain of the entire chromosome 17 (three cases); or 3) normal copy number of chromosome 17 (three cases). GAS and ERBB2 protein expression was studied by Western immunoblotting from gastric cancer cell lines with or without gain at 17q12-q21 as well as a breast cancer cell line with ERBB2 amplification. Our results showed that simultaneous 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 same region of the nucleus. Overexpression of GAS and ERBB2 was observed 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 unique 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 amplification. This indicates that the formation of an amplicon, in which both the GAS and the ERBB2 genes are amplified, might be unique in gastric cancer, especially in its intestinal type, and that simultaneous amplification of both genes is important to the tumorigenesis of intestinal 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.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Vidgren
authors.forename: A
authors.initials: A
authors.lastname: Varis
authors.forename: A
authors.initials: A
authors.lastname: Kokkola
authors.forename: O
authors.initials: O
authors.lastname: Monni
authors.forename: P
authors.initials: P
authors.lastname: Puolakkainen
authors.forename: S
authors.initials: S
authors.lastname: Nordling
authors.forename: F
authors.initials: F
authors.lastname: Forozan
authors.forename: A
authors.initials: A
authors.lastname: Kallioniemi
authors.forename: M L
authors.initials: ML
authors.lastname: Vakkari
authors.forename: E
authors.initials: E
authors.lastname: Kivilaakso
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D001943:Breast Neoplasms; D002277:Carcinoma / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005755:Gastrins / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D005755:Gastrins; D018719:Erb-b2 Receptor Tyrosine Kinases