title: Lack of MEN1 gene mutations in 27 sporadic insulinomas.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Heinrich-Heine-University, Düsseldorf; Institute for Hormone and Fertility Research at the University of Hamburg, Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Cupisti
authors.forename: W
authors.initials: W
authors.lastname: Höppner
authors.forename: C
authors.initials: C
authors.lastname: Dotzenrath
authors.forename: D
authors.initials: D
authors.lastname: Simon
authors.forename: I
authors.initials: I
authors.lastname: Berndt
authors.forename: H D
authors.initials: HD
authors.lastname: Röher
authors.forename: P E
authors.initials: PE
authors.lastname: Goretzki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005091:Exons; D005260:Female; D016147:Genes, Tumor Suppressor; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007340:Insulinoma / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000601:surgery; D011518:Proto-Oncogene Proteins; D015203:Reproducibility of Results
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins