PMID- 10759881
OWN - NLM
STAT- MEDLINE
DCOM- 20000531
LR  - 20190826
IS  - 0014-2972 (Print)
IS  - 0014-2972 (Linking)
VI  - 30
IP  - 4
DP  - 2000 Apr
TI  - Lack of MEN1 gene mutations in 27 sporadic insulinomas.
PG  - 325-9
AB  - BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant 
      familial cancer syndrome characterized by tumours of the parathyroids, anterior 
      pituitary gland and endocrine pancreas. Since the cloning of the MEN1 gene 
      (encoding menin) on chromosome 11q13 by Chandrasekharappa et al. in 1997, it has 
      become possible to identify mutations that are responsible. We examined whether 
      MEN1 gene mutations are present in sporadic insulinomas, a rare sporadic tumour 
      that is seen more frequently in patients with the MEN 1 syndrome. PATIENTS AND 
      METHODS: We sequenced the coding part of the MEN1 gene (exons 2-10) in tumour 
      tissue of 27 patients suffering from an insulinoma (24 benign, three malignant). 
      To validate our methods we also examined tumour tissue from five patients with 
      primary hyperparathyroidism (HPT) at a younger age and/or multiple gland disease, 
      with increased risk of MEN 1. RESULTS: We found no mutations in the nine coding 
      exons of the MEN1 gene in the insulinoma tissues. We could confirm three benign 
      polymorphisms (S145S, R171Q, D418D) reported previously. In the control patients 
      we found two new point mutations (one mis-sense, one non-sense mutation) and one 
      deletion. CONCLUSION: Mutations of the MEN1 gene do not play an important role in 
      the pathogenesis of sporadic insulinomas. Therefore genetic screening is not cost 
      effective in sporadic insulinoma patients without other indicators of MEN 1. 
      Patients with primary HPT at a younger age and/or multiple gland disease should 
      be screened for MEN1 gene mutations.
FAU - Cupisti, K
AU  - Cupisti K
AD  - Heinrich-Heine-University, Dusseldorf; Institute for Hormone and Fertility 
      Research at the University of Hamburg, Hamburg, Germany.
FAU - Hoppner, W
AU  - Hoppner W
FAU - Dotzenrath, C
AU  - Dotzenrath C
FAU - Simon, D
AU  - Simon D
FAU - Berndt, I
AU  - Berndt I
FAU - Roher, H D
AU  - Roher HD
FAU - Goretzki, P E
AU  - Goretzki PE
LA  - eng
PT  - Journal Article
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Substitution
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - Exons
MH  - Female
MH  - *Genes, Tumor Suppressor
MH  - Genetic Carrier Screening
MH  - Genetic Predisposition to Disease
MH  - Homozygote
MH  - Humans
MH  - Insulinoma/*genetics/surgery
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Neoplasm Proteins/*genetics
MH  - Pancreatic Neoplasms/*genetics/surgery
MH  - *Proto-Oncogene Proteins
MH  - Reproducibility of Results
EDAT- 2000/04/12 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/04/12 09:00
PHST- 2000/04/12 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/04/12 09:00 [entrez]
AID - eci620 [pii]
AID - 10.1046/j.1365-2362.2000.00620.x [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2000 Apr;30(4):325-9. doi: 10.1046/j.1365-2362.2000.00620.x.