title: Unique gene expression profile associated with an early-onset multiple endocrine neoplasia (MEN1)-associated pituitary adenoma.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 1 (MEN1) is caused by mutations in the menin (MEN1) gene. The mechanism(s) by which MEN1 mutations lead to pituitary tumor formation remain(s) unknown.
  
  
  OBJECTIVE
  The aim of the study was to identify the pediatric MEN1-associated pituitary tumor transcriptome.
  
  
  METHODS
  A patient harboring a MEN1 mutation (c.525C>G; p.H139D) who presented with an early-onset mammosomatotroph pituitary adenoma was studied. Microarray analysis was performed in the tumor sample and compared with the profile observed in normal pituitaries and in a sporadic mammosomatotropinoma. Validation of the microarray results was performed using quantitative real-time PCR and immunohistochemical analysis for selected genes.
  
  
  RESULTS
  In the MEN1-associated pituitary adenoma, 59 and 24 genes were found to be significantly up- and down-regulated, respectively. The up-regulated genes included those involved in cell growth and maintenance, apoptosis, growth arrest, and tumorigenesis. Moreover, we observed decreased expression in genes neuroendocrine in nature and related to growth or apoptosis. Only 21 of the 59 genes differentially expressed in the MEN1-associated adenoma showed a similar expression profile to that seen in the sporadic mammosomatotropinoma; for some genes an opposite expression profile was observed.
  
  
  CONCLUSIONS
  We identified changes in the transcriptome that occur in pituitary GH- and PRL-producing cells after the loss of menin expression; some of the gene changes are necessary for tumor evolution, and others may be tertiary. Nevertheless, the rare overlap between the expression profiles of the MEN1 tumor vs. that of its sporadic counterpart suggests that these tumors evolve along different molecular pathways.
authors.affiliation: Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Building 10, CRC, Room 1-3330, 10 Center Drive, MSC1103, Bethesda, Maryland 20892, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Farrell
authors.forename: Monalisa F
authors.initials: MF
authors.lastname: Azevedo
authors.forename: Dalia L
authors.initials: DL
authors.lastname: Batista
authors.forename: Alastair
authors.initials: A
authors.lastname: Smith
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourdeau
authors.forename: Anelia
authors.initials: A
authors.lastname: Horvath
authors.forename: Margaret
authors.initials: M
authors.lastname: Boguszewski
authors.forename: Martha
authors.initials: M
authors.lastname: Quezado
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology