title: Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene.
abstract: OBJECTIVE
  This study determined whether genomic amplification of HER-2/neu or mutations of the p53 and ras genes were present in gastrinomas.
  
  
  BACKGROUND
  Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto-oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome.
  
  
  METHODS
  The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present.
  
  
  RESULTS
  Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes.
  
  
  CONCLUSIONS
  Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston.
authors.forename: B M
authors.initials: BM
authors.lastname: Evers
authors.forename: P L
authors.initials: PL
authors.lastname: Rady
authors.forename: K
authors.initials: K
authors.lastname: Sandoval
authors.forename: I
authors.initials: I
authors.lastname: Arany
authors.forename: S K
authors.initials: SK
authors.lastname: Tyring
authors.forename: R L
authors.initials: RL
authors.lastname: Sanchez
authors.forename: W H
authors.initials: WH
authors.lastname: Nealon
authors.forename: C M
authors.initials: CM
authors.lastname: Townsend
authors.forename: J C
authors.initials: JC
authors.lastname: Thompson
mesh_terms: D001483:Base Sequence; D005260:Female; D015408:Gastrinoma / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D014407:Tumor Cells, Cultured
chemical_list: D009856:Oncogene Proteins, Viral; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human