Review on Multiple endocrine neoplasia type 1 (MEN1), with data on clinics, and the genes involved

Calender, A

Atlas of Genetics and Cytogenetics in Oncology and Haematology

A Calender

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Multiple endocrine neoplasia type 1 (MEN1)

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Cancer Prone Disease Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2000; 4(2)  
 
92 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
Multiple endocrine neoplasia type 1 (MEN1) 
Alain Calender 
Service de génétique moléculaire et médicale, hôpital Edouard-Herriot, bâtiment B7, 5, place d'Arsonval, 
69437 Lyon 03, France (AC) 
 
Published in Atlas Database: March 2000 
Online updated version : http://AtlasGeneticsOncology.org/Kprones/MEN1KproneID10008.html 
DOI: 10.4267/2042/37630 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2000 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Alias: Wermer's syndrome 
Note: Multiple Endocrine Neoplasia type 1 or 
Wermer's syndrome (MEN1) is a complex disease 
predisposing to a variety of endocrine tumors 
multifocal and/or bilateral localization and 
uncommonly to non-endocrine tumors mainly of the 
skin and central nervous system. 
Inheritance: An autosomal dominant disorder with 
high penetrance (increasing with age: 90% by age 50 
years) but variable expressivity (with 
phenotype/genotype correlations); frequency is unkown 
but estimated between 1/50000 and 1/30000. 
Clinics 
Phenotype and clinics 
Onset of the disease occurs commonly between 15 and 
40 years and most patients (90-100%) present primary 
hyperparathyroidism related to multiglandular 
hyperplasia and/or adenomas; other endocrine lesions 
and relative percentages are neuroendocrine tumors of 
the pancreas (either functionnal such as gastrinomas, 
insulinoma, and more rarely glucagonoma, VIPoma or 
non functionnal) (50-70%), pituitary adenoma (20-
40%), adrenocortical hyperplasia, adenomas or cancers 
(20-70%) and thymic/bronchial neuroendocrine tumors 
(5-10%); cutaneous lesions, such as angiofibromas, 
collagenomas, lentiginosis, melanocytic lesions and 
lipoma might occur in 5-10% of MEN1 patients; less 
common lesions are infratentorial papillary 
ependymoma, rhabdomyosarcoma and 
leiomyosarcoma, and renal and thyroid cancers. 
Neoplastic risk 
Pancreatic neuroendocrine tumors such as gastrinoma 
have malignant evolution in 30 to 50% of the cases. 
Insulinoma might be frequently benign. Most agressive 
tumors are glucagonoma and VIPoma (VIP: vasoactive 
intestinal peptide) in pancreas and some tumors 
occuring in the adrenal cortex. 
Pituitary adenomas in MEN1 are classical benign 
lesions but complications might be related to local 
nervous compression by the tumor. 
Parathyroid adenomas in MEN1 remain benign lesions. 
Cutaneous and CNS (Central Nervous System) lesions 
in MEN1 might be malignant in a few cases. Strikingly, 
melanomas, ependymomas and rare astrocytomas 
observed in the MEN1 context have better prognosis 
than the same lesions occuring sporadically. 
Treatment 
Parathyroids: the recommended procedure is 3 and half 
parathyroidectomy and cautious exploration of the 
thymic tissues in which ectopic adenomas and/or 
carcinoids (neuroendocrine tumors) have been 
described. 
Pancreas: in most cases (insulinoma, glucagonomas, > 
2cm non functionnal tumors, surgery is a best 
procedure and might be duodenopancreactomy in the 
heavy cases; nevertheless, in gastrinomas and non 
functionnal small tumors identified by US endoscopy, 
the best procedure is the medical (antiacid) treatmn  
and a careful follow-up of patients. 
Pituitary adenomas: the treatment is the same than for 
sporadic lesions. 
Adrenal glands tumors: surgery is the best 
recommended procedure when lesions are clearly 
identified by imagery. 
 
Multiple endocrine neoplasia type 1 (MEN1) Calender A 
 
 
 
 
 
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Thymic/bronchial carcinoids: they must be cured by 
surgery because they are malignant and alter prognosis 
in MEN1 patients. 
Prognosis 
according to the severity of the disease in a given 
patient, and to the quality of a regular follow up; mean 
age at death is relatively similar to that of the general 
population; nevertheless, death may occur early in ife 
(10 to 50 year) due to the complications of hormonal 
secretions by tumors (hemorrhagic ulcers, malignant 
hypercalcaemia, carcinoid syndromes) or evolution of 
the maligant process (pancreatic neuroendocrine 
tumors and thoracic carcinoids): 50 years; a 
presymptomatic diagnosis improves survival data and
might prevent earlier the main causes of death in this 
disease. 
Genes involved and proteins 
MEN1 
Location 
11q13 
DNA/RNA 
Description: 10 exons. 
Transcription: Different splicing. 
Protein 
Description: 610 amino-acids, 67 Kda; contains two 
nuclear localization signals. 
Expression: Wide. 
Function: Growth-suppressor gene. 
Mutations 
Germinal: Causes multiple endocrine neoplasia type 1. 
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Multiple endocrine neoplasia type 1 (MEN1) Calender A 
 
 
 
 
 
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This article should be referenced as such: 
Calender A. Multiple endocrine neoplasia type 1 (MEN1). Atlas 
Genet Cytogenet Oncol Haematol. 2000; 4(2):92-94. 


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