PMID- 17135306
OWN - NLM
STAT- MEDLINE
DCOM- 20070529
LR  - 20240316
IS  - 0017-5749 (Print)
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 56
IP  - 5
DP  - 2007 May
TI  - Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell 
      neoplasms and their precursor lesions.
PG  - 637-44
AB  - BACKGROUND: Patients with a multiple endocrine neoplasia type 1 (MEN1)-associated 
      Zollinger-Ellison syndrome (ZES) show multifocal duodenal gastrinomas and 
      precursor lesions. AIMS: To test these lesions for loss of heterozygosity (LOH) 
      of the MEN1 gene locus on chromosome 11q13, and to investigate whether the 
      MEN1-related endocrine cell changes also involved somatostatin cells. MATERIAL 
      AND METHODS: Tissue specimens from six patients with MEN1 and ZES were analysed 
      by immunohistochemistry and immunofluorescence. LOH analysis was performed by 
      fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene 
      locus and the centromere 11 (C11) region. For simultaneous analysis of hormones 
      and allelic deletions, a combined FISH/immunofluorescence protocol was 
      established. RESULTS: 28 of a total of 33 duodenal neuroendocrine tumours (NETs) 
      were gastrin-producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. 
      Five of the NETs were somatostatin-expressing tumours, two revealing LOH. Allelic 
      loss was detected in tumours as small as 300 microm (gastrin) and 400 microm 
      (somatostatin) in diameter. The gastrin-producing tumours showed different 
      deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to 
      those of the gastrin cells, were present in all patients. The hyperplastic 
      lesions of both cell lines consistently retained both 11q13 alleles. CONCLUSIONS: 
      Allelic deletion of the MEN1 gene may reflect a pivotal event in the development 
      of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients 
      with MEN1. The observation of distinct deletion patterns in small synchronous 
      tumours supports the concept that each gastrin-producing tumour in an individual 
      MEN1 patient arises from an independent cell clone.
FAU - Anlauf, M
AU  - Anlauf M
AD  - Department of Pathology W, University of Kiel, Michaelisstr 11, 24105 Kiel, 
      Germany. manlauf@path.uni-kiel.de
FAU - Perren, A
AU  - Perren A
FAU - Henopp, T
AU  - Henopp T
FAU - Rudolf, T
AU  - Rudolf T
FAU - Garbrecht, N
AU  - Garbrecht N
FAU - Schmitt, A
AU  - Schmitt A
FAU - Raffel, A
AU  - Raffel A
FAU - Gimm, O
AU  - Gimm O
FAU - Weihe, E
AU  - Weihe E
FAU - Knoefel, W T
AU  - Knoefel WT
FAU - Dralle, H
AU  - Dralle H
FAU - Heitz, Ph U
AU  - Heitz PU
FAU - Komminoth, P
AU  - Komminoth P
FAU - Kloppel, G
AU  - Kloppel G
LA  - eng
PT  - Journal Article
DEP - 20061129
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
CIN - Gut. 2007 May;56(5):606-7. PMID: 17440178
MH  - Adult
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Duodenal Neoplasms/*genetics/pathology
MH  - Female
MH  - Gastrinoma/*genetics/pathology
MH  - Humans
MH  - Hyperplasia/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Precancerous Conditions/genetics/pathology
MH  - Proto-Oncogene Proteins/*genetics
MH  - Zollinger-Ellison Syndrome/genetics/pathology
PMC - PMC1942169
COIS- Competing interests: None.
EDAT- 2006/12/01 09:00
MHDA- 2007/05/30 09:00
PMCR- 2010/05/01
CRDT- 2006/12/01 09:00
PHST- 2006/12/01 09:00 [pubmed]
PHST- 2007/05/30 09:00 [medline]
PHST- 2006/12/01 09:00 [entrez]
PHST- 2010/05/01 00:00 [pmc-release]
AID - gut.2006.108910 [pii]
AID - gt108910 [pii]
AID - 10.1136/gut.2006.108910 [doi]
PST - ppublish
SO  - Gut. 2007 May;56(5):637-44. doi: 10.1136/gut.2006.108910. Epub 2006 Nov 29.