PMID- 12030908
OWN - NLM
STAT- MEDLINE
DCOM- 20020716
LR  - 20190813
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 56
IP  - 5
DP  - 2002 May
TI  - Increased menin expression in sporadic pituitary adenomas.
PG  - 589-94
AB  - 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. 
      PATIENTS AND MEASUREMENTS: 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.
FAU - Wrocklage, Christian
AU  - Wrocklage C
AD  - Institute of Neuropathology, University Hospital, Domagkstrasse 19, D-48129 
      Munster, Germany.
FAU - Gold, Heidrun
AU  - Gold H
FAU - Hackl, Wolfgang
AU  - Hackl W
FAU - Buchfelder, Michael
AU  - Buchfelder M
FAU - Fahlbusch, Rudolf
AU  - Fahlbusch R
FAU - Paulus, Werner
AU  - Paulus W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adenoma/*metabolism
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Female
MH  - Gene Deletion
MH  - Humans
MH  - Image Processing, Computer-Assisted
MH  - Immunoblotting
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation, Missense
MH  - Neoplasm Proteins/analysis/*genetics
MH  - Pituitary Neoplasms/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Sequence Analysis, DNA
EDAT- 2002/05/29 10:00
MHDA- 2002/07/18 10:01
CRDT- 2002/05/29 10:00
PHST- 2002/05/29 10:00 [pubmed]
PHST- 2002/07/18 10:01 [medline]
PHST- 2002/05/29 10:00 [entrez]
AID - 1516 [pii]
AID - 10.1046/j.1365-2265.2002.01516.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2002 May;56(5):589-94. doi: 
      10.1046/j.1365-2265.2002.01516.x.