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Multiple endocrine neoplasia type 1 (MEN1)

Written2000-03Alain Calender
Service de genetique moleculaire et medicale, hopital Edouard-Herriot, batiment B7, 5, place d'Arsonval, 69437 Lyon 03, France

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Identity

Other namesWermer's syndrome
Atlas_Id 10008
Genes implicated inMEN1  
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 yrs) 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 yrs 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 classicla 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 Nervos 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) treatment and a careful follow-up of patients.
  • pituitary adenomas : the treatment is the same as for sporadic lesions
  • adrenal glands tumors : surgery is the best recommended procedure when lesions are clearly identified by imagery
  • 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 life (10 to 50yr) 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 yrs; a presymptomatic diagnosis improves survival data and might prevent earlier the main causes of death in this disease

    Genes involved and Proteins

    Gene NameMEN1
    Location 11q13
    DNA/RNA
    Description 10 exons
    Transcription different splicings
    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

    Bibliography

    Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription.
    Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL
    Cell. 1999 ; 96 (1) : 143-152.
    PMID 9989505
     
    Characterization of mutations in patients with multiple endocrine neoplasia type 1.
    Bassett JH, Forbes SA, Pannett AA, Lloyd SE, Christie PT, Wooding C, Harding B, Besser GM, Edwards CR, Monson JP, Sampson J, Wass JA, Wheeler MH, Thakker RV
    American journal of human genetics. 1998 ; 62 (2) : 232-244.
    PMID 9463336
     
    [Clinicogenetic study of MEN1: recent physiopathological data and clinical applications. Study Group of Multiple Endocrine Neoplasia (GENEM)]
    Calender A, Giraud S, Porchet N, Gaudray P, Cadiot G, Mignon M
    Annales d'endocrinologie. 1998 ; 59 (6) : 444-451.
    PMID 10189986
     
    Positional cloning of the gene for multiple endocrine neoplasia-type 1.
    Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weisemann J, Boguski MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL, Marx SJ
    Science (New York, N.Y.). 1997 ; 276 (5311) : 404-407.
    PMID 9103196
     
    Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1.
    Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M
    Archives of dermatology. 1997 ; 133 (7) : 853-857.
    PMID 9236523
     
    A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation.
    Giraud S, Choplin H, Teh BT, Lespinasse J, Jouvet A, Labat-Moleur F, Lenoir G, Hamon B, Hamon P, Calender A
    The Journal of clinical endocrinology and metabolism. 1997 ; 82 (10) : 3487-3492.
    PMID 9329390
     
    Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders.
    Giraud S, Zhang CX, Serova-Sinilnikova O, Wautot V, Salandre J, Buisson N, Waterlot C, Bauters C, Porchet N, Aubert JP, Emy P, Cadiot G, Delemer B, Chabre O, Niccoli P, Leprat F, Duron F, Emperauger B, Cougard P, Goudet P, Sarfati E, Riou JP, Guichard S, Rodier M, Meyrier A, Caron P, Vantyghem MC, Assayag M, Peix JL, Pugeat M, Rohmer V, Vallotton M, Lenoir G, Gaudray P, Proye C, Conte-Devolx B, Chanson P, Shugart YY, Goldgar D, Murat A, Calender A
    American journal of human genetics. 1998 ; 63 (2) : 455-467.
    PMID 9683585
     
    Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin.
    Huang SC, Zhuang Z, Weil RJ, Pack S, Wang C, Krutzsch HC, Pham TA, Lubensky IA
    Laboratory investigation; a journal of technical methods and pathology. 1999 ; 79 (3) : 301-310.
    PMID 10092066
     
    AP-1 function and regulation.
    Karin M, Liu Z, Zandi E
    Current opinion in cell biology. 1997 ; 9 (2) : 240-246.
    PMID 9069263
     
    Multiple endocrine neoplasia type 1 associated with spinal ependymoma.
    Kato H, Uchimura I, Morohoshi M, Fujisawa K, Kobayashi Y, Numano F, Goseki N, Endo M, Tamura A, Nagashima C
    Internal medicine (Tokyo, Japan). 1996 ; 35 (4) : 285-289.
    PMID 8739783
     
    Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma.
    Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjö M
    Nature. 1988 ; 332 (6159) : 85-87.
    PMID 2894610
     
    Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1.
    Lemmens I, Van de Ven WJ, Kas K, Zhang CX, Giraud S, Wautot V, Buisson N, De Witte K, Salandre J, Lenoir G, Pugeat M, Calender A, Parente F, Quincey D, Gaudray P, De Wit MJ, Lips CJ, Höppener JW, Khodaei S, Grant AL, Weber G, Kytölä S, Teh BT, Farnebo F, Thakker RV
    Human molecular genetics. 1997 ; 6 (7) : 1177-1183.
    PMID 9215690
     
    Late outcome of 304 consecutive patients with multiple gland enlargement in primary hyperparathyroidism treated by conservative surgery.
    Proye C, Carnaille B, Quievreux JL, Combemale F, Oudar C, Lecomte-Houcke M
    World journal of surgery. 1998 ; 22 (6) : 526-529.
    PMID 9597923
     
    The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized?
    Shepherd JJ
    Archives of surgery (Chicago, Ill. : 1960). 1991 ; 126 (8) : 935-952.
    PMID 1677802
     
    Adrenal lesion in multiple endocrine neoplasia type 1.
    Skogseid B, Rastad J, Gobl A, Larsson C, Backlin K, Juhlin C, Akerström G, Oberg K
    Surgery. 1995 ; 118 (6) : 1077-1082.
    PMID 7491526
     
    Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.
    Teh BT, Kytölä S, Farnebo F, Bergman L, Wong FK, Weber G, Hayward N, Larsson C, Skogseid B, Beckers A, Phelan C, Edwards M, Epstein M, Alford F, Hurley D, Grimmond S, Silins G, Walters M, Stewart C, Cardinal J, Khodaei S, Parente F, Tranebjaerg L, Jorde R, Salmela P
    The Journal of clinical endocrinology and metabolism. 1998 ; 83 (8) : 2621-2626.
    PMID 9709921
     
    Clinical studies of multiple endocrine neoplasia type 1 (MEN1)
    Trump D, Farren B, Wooding C, Pang JT, Besser GM, Buchanan KD, Edwards CR, Heath DA, Jackson CE, Jansen S, Lips K, Monson JP, O'Halloran D, Sampson J, Shalet SM, Wheeler MH, Zink A, Thakker RV
    QJM : monthly journal of the Association of Physicians. 1996 ; 89 (9) : 653-669.
    PMID 8917740
     
    ENDOCRINE ADENOMATOSIS AND PEPTIC ULCER IN A LARGE KINDRED. INHERITED MULTIPLE TUMORS AND MOSAIC PLEIOTROPISM IN MAN.
    WERMER P
    The American journal of medicine. 1963 ; 35 : 205-212.
    PMID 14057623
     

    Citation

    This paper should be referenced as such :
    Calender, A
    Multiple endocrine neoplasia type 1 (MEN1)
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(2):92-94.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Tumors/MEN1KproneID10008.html

    External links

    OMIM131100
    OrphanetMultiple endocrine neoplasia type 1
    MeSHD018761  
    MedGenD018761  
    UMLSC0025267  
    ICD-10D44.8  
    HGMD120173
    Other databaseMEN1 mutation database
    Other databaseGENEM Scientific network
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


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