Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas

Alexander Vortmeyer, Irina A. Lubensky, Franz Fogt, W. Marston Linehan, Urmila Khettry, Zhengping Zhuang

Research output: Contribution to journalArticle

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Abstract

An association between pancreatic microcystic (serous) adenomas (MCAs) and von Hippel-Lindau (VHL) disease has been suggested. However, genetic alterations of the VHL gene in MCAs of the pancreas have never been reported. In this study, we performed genetic analysis of 12 pancreatic MCAs. In 2 cases, VHL disease was documented clinically, and 10 cases were sporadic. For LOH analysis, tumor and normal pancreatic cells were procured from formalin- fixed, paraffin-embedded material using tissue microdissection. After DNA extraction, the samples were amplified by polymerase chain reaction using the polymorphic markers D3S2452, D3S1110, D3S192, and D3S656. In addition, the sporadic tumors were analyzed for VHL gene mutations using probes 3b/10b and K55/K56. Both MCAs associated with VHL disease showed LOH with at least one of the microsatellite markers tested. Among the 10 sporadic cases, 7 tumors showed LOH at the VHL gene locus. A somatic VHL gene mutation on exon 2 was documented in one sporadic case. The study provides the first direct genetic evidence for the role of the VHL gene in MCA tumorigenesis. Furthermore, VHL gene alterations may be detected in both VHL-associated and sporadic pancreatic MCAs.

Original languageEnglish (US)
Pages (from-to)951-956
Number of pages6
JournalAmerican Journal of Pathology
Volume151
Issue number4
StatePublished - Oct 1 1997
Externally publishedYes

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Sequence Deletion
Tumor Suppressor Genes
Adenoma
von Hippel-Lindau Disease
Genes
Neoplasms
Microdissection
Mutation
Paraffin
Microsatellite Repeats
Formaldehyde
Pancreatic adenoma
Pancreas
Exons
Carcinogenesis
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. / Vortmeyer, Alexander; Lubensky, Irina A.; Fogt, Franz; Linehan, W. Marston; Khettry, Urmila; Zhuang, Zhengping.

In: American Journal of Pathology, Vol. 151, No. 4, 01.10.1997, p. 951-956.

Research output: Contribution to journalArticle

Vortmeyer, Alexander ; Lubensky, Irina A. ; Fogt, Franz ; Linehan, W. Marston ; Khettry, Urmila ; Zhuang, Zhengping. / Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. In: American Journal of Pathology. 1997 ; Vol. 151, No. 4. pp. 951-956.
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