The MEN1 gene and pituitary tumours

Horm Res. 2009 Apr;71 Suppl 2(Suppl 2):131-8. doi: 10.1159/000192450. Epub 2009 Apr 29.

Abstract

Sporadic multiple endocrine neoplasia type 1 (MEN1) is defined as the occurrence of tumours in two of three main endocrine tissue types: parathyroid, pituitary and pancreaticoduodenal. A prolactinoma variant or Burin variant of MEN1 was found to occur in three large kindreds, with more prolactinomas and fewer gastrinomas than typical MEN1. MEN1 tumours differ from common tumours by showing features from the MEN1 gene (e.g. larger pituitary tumours). They also show various expressions of tumour multiplicity; however, pituitary tumour in MEN1 is usually solitary. Diagnosis in MEN1 carriers during childhood is not directed at cancers but at benign morbid tumours. Morbid prolactinoma occurred at the age of 5 years in one MEN1 individual; hence, this is the earliest age at which to recommend tumour surveillance in carriers. The MEN1 gene shows biallelic inactivation in 30% of some types of common variety endocrine tumours (e.g. parathyroid adenoma, gastrinoma, insulinoma and bronchial carcinoid), but in only 1-5% of common pituitary tumours. Heterozygous knockout of MEN1 in mice provides a robust model of MEN1 and has been found to support further research on anti-angiogenesis therapy for pituitary tumours. The rarity of MEN1 mutations in some MEN1-like states aids the identification of other mutated genes, such as AIP, HRPT2 and p27(Kip1). We present recent clinical and basic findings about the MEN1 gene, particularly concerning hereditary vs. common variety pituitary tumours.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Knockout Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Multiple Endocrine Neoplasia Type 1 / metabolism*
  • Mutation
  • Prolactinoma / genetics
  • Prolactinoma / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • CDC73 protein, human
  • CDKN1B protein, human
  • Cdkn1b protein, mouse
  • HRPT2 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • MEN1 protein, human
  • Men1 protein, mouse
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • aryl hydrocarbon receptor-interacting protein
  • Cyclin-Dependent Kinase Inhibitor p27