title: Increased menin expression in sporadic pituitary adenomas.
abstract: BACKGROUND
  Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour-suppressor gene are responsible for multiple endocrine neoplasia type 1, and menin, the MEN1 gene product, is usually downregulated or truncated in MEN1-associated adenomas. In contrast, exonic MEN1 mutations seem to be very rare in sporadic (MEN1-unrelated) pituitary adenomas, and it has been suggested that menin does not play a major role in these tumours. However, menin might be involved in sporadic adenoma tumorigenesis by downregulation through intronic mutations, epigenetic, posttranscriptional or posttranslational mechanisms.
  
  
  METHODS
  We screened MEN1 coding regions and flanking intronic sequences of 136 sporadic pituitary adenomas by temporal temperature gradient gel electrophoresis (TTGE) and studied menin expression by immunoblotting in 11 of these tumours.
  
  
  RESULTS
  Sequencing of DNAs showing aberrant migration on TTGE revealed five somatic MEN1 mutations, including two missense mutations (F134L, E530K), a 2-bp deletion in exon 10 (c.1567-1568del) leading to a premature stop codon, and two 3-bp deletions in intron 5 (g.5236-5238del, g.5237-5239del). These mutations have not been reported previously in studies analysing the MEN1 gene. Immunoblotting showed menin upregulation in all adenomas examined (including one case with a missense mutation) from 1.7-fold to 10.4-fold (mean, 4.2-fold) compared to non-neoplastic adenohypophysis.
  
  
  CONCLUSIONS
  Our data suggest that neither MEN1 mutations nor menin downregulation play a significant role in the development of sporadic pituitary adenomas.
authors.affiliation: Institute of Neuropathology, University Hospital, Domagkstrasse 19, D-48129 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wrocklage
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gold
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hackl
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fahlbusch
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D017422:Sequence Analysis, DNA
chemical_list: C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins