title: MSH2 and CXCR4 involvement in malignant VIPoma.
abstract: BACKGROUND
  Vasoactive intestinal polypeptide secreting tumors(VIPomas) are rare endocrine tumors of the pancreas with an estimated incidence of 0.1 per million per year. The molecular mechanisms that mediate development of VIPomas are poorly investigated and require definition.
  
  
  METHODS
  A genome- and gene expression analysis of specimens of a primary pancreatic VIPoma with hepatic metastases was performed. The primary tumor, the metastases, the corresponding healthy tissue of the liver, and the pancreas were compared with each other using oligonucleotide microarrays and loss of heterozygosity (LOH).
  
  
  RESULTS
  The results revealed multiple LOH events and several differentially expressed genes. Our finding of LOH and downregulation was conspicuous in the microarray analysis for the mismatch repair gene MSH2 in the primary pancreatic VIPoma tumor, the hepatic metastasis but not in the corresponding healthy tissue. Further a strong overexpression of the chemokine CXCR4 was detected in the hepatic metastases compared to its pancreatic primary. With a review of the literature we describe the molecular insights of metastatic development in VIPoma.
  
  
  CONCLUSIONS
  In VIPoma, defects in the mismatch repair system especially in MSH2 may contribute to carcinogenesis, and increased CXCR4 may be associated with liver metastasis.
authors.affiliation: Department of General, Visceral and Transplant Surgery, Tübingen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Müller
authors.forename: Susan
authors.initials: S
authors.lastname: Kupka
authors.forename: Ingmar
authors.initials: I
authors.lastname: Königsrainer
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.forename: Thomas
authors.initials: T
authors.lastname: Bock
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.forename: Frank
authors.initials: F
authors.lastname: Traub
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Derek
authors.initials: D
authors.lastname: Zieker
mesh_terms: D000368:Aged; D053843:DNA Mismatch Repair / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D003969:Vipoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein