title: X-chromosome loss of heterozygosity frequently occurs in gastrinomas and is correlated with aggressive tumor growth.
abstract: BACKGROUND
  Recent studies have shown that tumor growth, rather than hormone overproduction, is the leading cause of death among patients with gastrinomas and other malignant gastrointestinal endocrine tumors. No patient/laboratory characteristics accurately predict which tumors will exhibit aggressive growth. Furthermore, little is known regarding the molecular pathogenesis of these tumors. X-chromosome loss of heterozygosity (LOH) occurs in some nonendocrine tumors, and its presence can be associated with aggressive growth/decreased survival. Data on X-chromosome LOH in gastrointestinal endocrine tumors are conflicting. Therefore, the purpose of the current study was to determine whether X-chromosome LOH occurred in gastrinomas and, if so, whether it was correlated with tumor growth, tumor behavior, and/or prognosis.
  
  
  METHODS
  X chromosome allelotyping was performed using 12 microsatellite markers spaced throughout the chromosome using DNA from leukocytes and microdissected gastrinoma specimens from 16 female patients. The presence of X-chromosome LOH was analyzed for correlations with clinical and laboratory tumor characteristics as well as tumor growth characteristics.
  
  
  RESULTS
  Nine gastrinoma specimens (56%) had X-chromosome LOH, ranging from 6% to 23% at the 12 different loci studied. X-chromosome LOH was significantly associated with aggressive postoperative tumor growth, increased primary tumor size, and pancreatic primaries. In 6 tumor specimens, LOH occurred on Xp22.1-22.3 over a 28.4-centimorgan region.
  
  
  CONCLUSIONS
  X-chromosome LOH was common in gastrinoma specimens from female patients, and its presence was found to be a potentially useful molecular/genetic prognostic factor for aggressive growth.
authors.affiliation: Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yuan-Jia
authors.initials: YJ
authors.lastname: Chen
authors.forename: Alexander
authors.initials: A
authors.lastname: Vortmeyer
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Fathia
authors.initials: F
authors.lastname: Gibril
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D041321:Chromosomes, Human, X / Q000235:genetics*; D004247:DNA / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D015408:Gastrinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D015043:Zollinger-Ellison Syndrome / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D004247:DNA