PMID- 24389729
OWN - NLM
STAT- MEDLINE
DCOM- 20150122
LR  - 20140507
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 21
IP  - 3
DP  - 2014 Jun
TI  - Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine 
      neoplasia type 1: natural history and function of menin in tumorigenesis.
PG  - R121-42
LID - 10.1530/ERC-13-0482 [doi]
AB  - Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of 
      function of its protein product menin. In keeping with its tumor suppressor 
      function in endocrine tissues, the majority of the MEN1-related neuroendocrine 
      tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic 
      NETs, MEN1 mutations and LOH are also reported, indicating common pathways in 
      tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in 
      MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on 
      natural history is limited, but disease-related mortality is low. thNETs have a 
      high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost 
      universally found at pathology, and associated with precursor lesions. 
      Gastrinomas are usually located in the duodenal submucosa while other dpNETs are 
      predominantly pancreatic. dpNETs are an important determinant of MEN1-related 
      survival, with an estimated 10-year survival of 75%. Survival differs between 
      subtypes and apart from tumor size there are no known prognostic factors. Natural 
      history of nonfunctioning pancreatic NETs needs to be redefined because of 
      increased detection of small tumors. MEN1-related gastrinomas seem to behave 
      similar to their sporadic counterparts, while insulinomas seem to be more 
      aggressive. Investigations into the molecular functions of menin have led to new 
      insights into MEN1-related tumorigenesis. Menin is involved in gene 
      transcription, both as an activator and repressor. It is part of 
      chromatin-modifying protein complexes, indicating involvement of epigenetic 
      pathways in MEN1-related NET development. Future basic and translational research 
      aimed at NETs in large unbiased cohorts will clarify the role of menin in NET 
      tumorigenesis and might lead to new therapeutic options.
FAU - Pieterman, C R C
AU  - Pieterman CR
AD  - Division of Internal Medicine and Dermatology, Department of Internal Medicine, 
      University Medical Center Utrecht, Internal post number L.00.408, PO Box 85500, 
      3508 GA Utrecht, The Netherlands Division of Biomedical Genetics, Department of 
      Molecular Cancer Research Division of Surgical Specialties, Department of 
      Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Conemans, E B
AU  - Conemans EB
FAU - Dreijerink, K M A
AU  - Dreijerink KM
FAU - de Laat, J M
AU  - de Laat JM
FAU - Timmers, H Th M
AU  - Timmers HT
FAU - Vriens, M R
AU  - Vriens MR
FAU - Valk, G D
AU  - Valk GD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140506
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Cell Transformation, Neoplastic/*pathology
MH  - Duodenal Neoplasms/metabolism/*pathology
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 1/metabolism/*pathology
MH  - Neoplasms, Multiple Primary/metabolism/*pathology
MH  - Neuroendocrine Tumors/metabolism/*pathology
MH  - Pancreatic Neoplasms/metabolism/*pathology
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Thoracic Neoplasms/metabolism/*pathology
OTO - NOTNLM
OT  - MEN1
OT  - duodenopancreatic NET
OT  - epigenetics
OT  - lung NET
OT  - menin
OT  - multiple endocrine neoplasia type 1
OT  - natural history
OT  - neuroendocrine tumors
OT  - pancreatic NET
OT  - thymic NET
EDAT- 2014/01/07 06:00
MHDA- 2015/01/23 06:00
CRDT- 2014/01/07 06:00
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2015/01/23 06:00 [medline]
AID - ERC-13-0482 [pii]
AID - 10.1530/ERC-13-0482 [doi]
PST - epublish
SO  - Endocr Relat Cancer. 2014 May 6;21(3):R121-42. doi: 10.1530/ERC-13-0482. Print 
      2014 Jun.