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X-chromosome loss of heterozygosity frequently occurs in gastrinomas and is correlated with aggressive tumor growth.

AbstractBACKGROUND:
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.
AuthorsYuan-Jia Chen, Alexander Vortmeyer, Zhengping Zhuang, Fathia Gibril, Robert T Jensen
JournalCancer (Cancer) Vol. 100 Issue 7 Pg. 1379-87 (Apr 01 2004) ISSN: 0008-543X [Print] United States
PMID15042671 (Publication Type: Journal Article)
Chemical References
  • DNA
Topics
  • Adolescent
  • Adult
  • Chromosomes, Human, X (genetics)
  • DNA (analysis)
  • Disease-Free Survival
  • Female
  • Gastrinoma (genetics, pathology, surgery)
  • Humans
  • Loss of Heterozygosity
  • Microsatellite Repeats
  • Middle Aged
  • Pancreatic Neoplasms (genetics, pathology, surgery)
  • Polymerase Chain Reaction
  • Zollinger-Ellison Syndrome (genetics, pathology, surgery)

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