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.
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Authors | Yuan-Jia Chen, Alexander Vortmeyer, Zhengping Zhuang, Fathia Gibril, Robert T Jensen |
Journal | Cancer
(Cancer)
Vol. 100
Issue 7
Pg. 1379-87
(Apr 01 2004)
ISSN: 0008-543X [Print] United States |
PMID | 15042671
(Publication Type: Journal Article)
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Chemical References |
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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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