PMID- 21917868
OWN - NLM
STAT- MEDLINE
DCOM- 20111223
LR  - 20211020
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 96
IP  - 11
DP  - 2011 Nov
TI  - Unique gene expression profile associated with an early-onset multiple endocrine 
      neoplasia (MEN1)-associated pituitary adenoma.
PG  - E1905-14
LID - 10.1210/jc.2011-1127 [doi]
AB  - CONTEXT: 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. PATIENTS 
      AND 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.
FAU - Farrell, William E
AU  - Farrell WE
AD  - 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.
FAU - Azevedo, Monalisa F
AU  - Azevedo MF
FAU - Batista, Dalia L
AU  - Batista DL
FAU - Smith, Alastair
AU  - Smith A
FAU - Bourdeau, Isabelle
AU  - Bourdeau I
FAU - Horvath, Anelia
AU  - Horvath A
FAU - Boguszewski, Margaret
AU  - Boguszewski M
FAU - Quezado, Martha
AU  - Quezado M
FAU - Stratakis, Constantine A
AU  - Stratakis CA
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110914
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
SB  - IM
MH  - Child
MH  - Child, Preschool
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Pituitary Neoplasms/*genetics/pathology
PMC - PMC3205896
EDAT- 2011/09/16 06:00
MHDA- 2011/12/24 06:00
PMCR- 2012/11/01
CRDT- 2011/09/16 06:00
PHST- 2011/09/16 06:00 [entrez]
PHST- 2011/09/16 06:00 [pubmed]
PHST- 2011/12/24 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - jc.2011-1127 [pii]
AID - 11-1127 [pii]
AID - 10.1210/jc.2011-1127 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2011 Nov;96(11):E1905-14. doi: 10.1210/jc.2011-1127. 
      Epub 2011 Sep 14.