PMID- 23933118
OWN - NLM
STAT- MEDLINE
DCOM- 20141023
LR  - 20220408
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 386
IP  - 1-2
DP  - 2014 Apr 5
TI  - Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4).
PG  - 2-15
LID - S0303-7207(13)00330-4 [pii]
LID - 10.1016/j.mce.2013.08.002 [doi]
AB  - Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors 
      involving two or more endocrine glands within a single patient. Four major forms 
      of MEN, which are autosomal dominant disorders, are recognized and referred to 
      as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to 
      mutations of a tyrosine kinase receptor encoded by the rearranged during 
      transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; 
      and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN 
      type is associated with the occurrence of specific tumors. Thus, MEN1 is 
      characterized by the occurrence of parathyroid, pancreatic islet and anterior 
      pituitary tumors; MEN2 is characterized by the occurrence of medullary thyroid 
      carcinoma (MTC) in association with phaeochromocytoma and parathyroid tumors; 
      MEN3 is characterized by the occurrence of MTC and phaeochromocytoma in 
      association with a marfanoid habitus, mucosal neuromas, medullated corneal fibers 
      and intestinal autonomic ganglion dysfunction, leading to megacolon; and MEN4, 
      which is also referred to as MENX, is characterized by the occurrence of 
      parathyroid and anterior pituitary tumors in possible association with tumors of 
      the adrenals, kidneys, and reproductive organs. This review will focus on the 
      clinical and molecular details of the MEN1 and MEN4 syndromes. The gene causing 
      MEN1 is located on chromosome 11q13, and encodes a 610 amino-acid protein, menin, 
      which has functions in cell division, genome stability, and transcription 
      regulation. Menin, which acts as scaffold protein, may increase or decrease gene 
      expression by epigenetic regulation of gene expression via histone methylation. 
      Thus, menin by forming a subunit of the mixed lineage leukemia (MLL) complexes 
      that trimethylate histone H3 at lysine 4 (H3K4), facilitates activation of 
      transcriptional activity in target genes such as cyclin-dependent kinase (CDK) 
      inhibitors; and by interacting with the suppressor of variegation 3-9 homolog 
      family protein (SUV39H1) to mediate H3K methylation, thereby silencing 
      transcriptional activity of target genes. MEN1-associated tumors harbor germline 
      and somatic mutations, consistent with Knudson's two-hit hypothesis. Genetic 
      diagnosis to identify individuals with germline MEN1 mutations has facilitated 
      appropriate targeting of clinical, biochemical and radiological screening for 
      this high risk group of patients for whom earlier implementation of treatments 
      can then be considered. MEN4 is caused by heterozygous mutations of CDNK1B which 
      encodes the 196 amino-acid CDK1 p27Kip1, which is activated by H3K4 methylation.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Headington, Oxford OX3 7LJ, United Kingdom. Electronic address: 
      rajesh.thakker@ndm.ox.ac.uk.
LA  - eng
GR  - G1000467/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130808
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Humans
MH  - Multiple Endocrine Neoplasia/genetics/*pathology
MH  - Multiple Endocrine Neoplasia Type 1/diagnosis/genetics/*pathology/therapy
MH  - Proto-Oncogene Proteins/metabolism
PMC - PMC4082531
OTO - NOTNLM
OT  - Histone methylation
OT  - Neuroendocrine tumors
OT  - Pancreatic islet
OT  - Parathyroid
OT  - Pituitary
OT  - Tumors
EDAT- 2013/08/13 06:00
MHDA- 2014/10/24 06:00
PMCR- 2014/04/05
CRDT- 2013/08/13 06:00
PHST- 2013/07/15 00:00 [received]
PHST- 2013/07/31 00:00 [revised]
PHST- 2013/07/31 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/10/24 06:00 [medline]
PHST- 2014/04/05 00:00 [pmc-release]
AID - S0303-7207(13)00330-4 [pii]
AID - 10.1016/j.mce.2013.08.002 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2014 Apr 5;386(1-2):2-15. doi: 10.1016/j.mce.2013.08.002. 
      Epub 2013 Aug 8.