PMID- 25210877
OWN - NLM
STAT- MEDLINE
DCOM- 20150116
LR  - 20220408
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 99
IP  - 11
DP  - 2014 Nov
TI  - Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with 
      MEN1 mutations affecting the CHES1 interacting MENIN domain.
PG  - E2387-91
LID - 10.1210/jc.2013-4432 [doi]
AB  - CONTEXT: Sixty to 80% of multiple endocrine neoplasia type 1 (MEN1) patients 
      develop pancreatic neuroendocrine neoplasias (pNENs), which reveal an aggressive 
      behavior in 10%-20% of patients. Causative MEN1 mutations in the interacting 
      domains of the encoded Menin protein directly alter its regulation abilities and 
      may influence the phenotype. OBJECTIVE: The objective of the study was the 
      evaluation of an association between MEN1 mutations in different interacting 
      domains of Menin and the phenotype of pNENs. DESIGN: This was a retrospective 
      analysis of a prospectively collected cohort of 71 genetically confirmed MEN1 
      patients at a tertiary referral center. MAIN OUTCOME MEASURES: Analysis of 
      patients' characteristics and clinical phenotype of pNENs regarding the mutation 
      type and its location in Menin interacting domains was measured. RESULTS: 
      Sixty-seven patients (93%) developed pNENs after a median follow-up of 134 
      months. Patients with mutations leading to loss of interaction (LOI) with the 
      checkpoint kinase 1 (CHES1) interacting domain codons (428-610) compared with 
      patients with mutations resulting in LOI with other domains (eg, JunD, Smad3) had 
      significantly higher rates of functioning pNENs (70% vs 34%), malignant pNENs 
      (59% vs 16%), and aggressive pNENs (37% vs 9%), respectively. Patients with 
      CHES1-LOI also had an increased pNEN-related mortality (20% vs 4.5%). Neither 
      gender, age, nor the ABO blood types were associated with the phenotype of pNENs. 
      CONCLUSIONS: MEN1 patients with MEN1 mutations leading to CHES1-LOI have a higher 
      risk of malignant pNENs with an aggressive course of disease and disease-related 
      death.
FAU - Bartsch, Detlef K
AU  - Bartsch DK
AD  - Departments of Visceral, Thoracic, and Vascular Surgery (D.K.B., E.P.S., M.A., 
      R.K., B.C., C.L.L., V.F., J.W.) and Gastroenterology (P.H.K.), Division of 
      Endocrinology and Diabetology, University Hospital Giessen and Marburg, Campus 
      Marburg, 35041 Marburg, Germany.
FAU - Slater, Emily P
AU  - Slater EP
FAU - Albers, Max
AU  - Albers M
FAU - Knoop, Richard
AU  - Knoop R
FAU - Chaloupka, Brunhilde
AU  - Chaloupka B
FAU - Lopez, Caroline L
AU  - Lopez CL
FAU - Fendrich, Volker
AU  - Fendrich V
FAU - Kann, Peter H
AU  - Kann PH
FAU - Waldmann, Jens
AU  - Waldmann J
LA  - eng
PT  - Journal Article
DEP - 20140911
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (FOXN3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Cell Cycle Proteins/*genetics
MH  - Child
MH  - Female
MH  - Forkhead Transcription Factors
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Mutation
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Neuroendocrine Tumors/*genetics/pathology
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Phenotype
MH  - Proto-Oncogene Proteins/*genetics
MH  - Repressor Proteins/*genetics
MH  - Retrospective Studies
MH  - Young Adult
EDAT- 2014/09/12 06:00
MHDA- 2015/01/17 06:00
CRDT- 2014/09/12 06:00
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2015/01/17 06:00 [medline]
AID - 10.1210/jc.2013-4432 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2014 Nov;99(11):E2387-91. doi: 10.1210/jc.2013-4432. 
      Epub 2014 Sep 11.