Variable clinical expression in patients with a germline MEN1 disease gene mutation: Clues to a genotype-phenotype correlation

Clinics

Volumn 67, Issue SUPPLEMENT, 2012, Pages 49-56

  Lips, Cornelis J ^a   Dreijerink, Koen M ^a   Höppener, Jo W ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Clinical Expression; Genotype Phenotype Correlation; MEN1; Menin; Multiple Endocrine Neoplasia type 1

Indexed keywords

MEN1 PROTEIN, HUMAN; ONCOPROTEIN;

ADENOMA; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETICS; HUMAN; HYPOPHYSIS TUMOR; METABOLISM; MULTIPLE ENDOCRINE NEOPLASIA; MUTATION; REVIEW;

ADENOMA; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GERM-LINE MUTATION; HUMANS; MULTIPLE ENDOCRINE NEOPLASIA TYPE 1; PITUITARY NEOPLASMS; PROTO-ONCOGENE PROTEINS;

EID: 84862069477     PISSN: 18075932     EISSN: None     Source Type: Journal    
DOI: 10.6061/clinics/2012(Sup01)10     Document Type: Review

References (92)

1. Wautot V, Vercherat C, Lespinasse J, Chambe B, Lenoir GM, Zhang CX, et al. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Hum Mutat. 2002;20(1):35-47, http://dx.doi.org/10.1002/humu.10092.
2. Kouvaraki MA, Lee JE, Shapiro SE, Gagel RF, Sherman SI, Sellin RV, et al. Genotype-phenotype analysis in multiple endocrine neoplasia type 1. Arch Surg. 2002;137(6):641-7, http://dx.doi.org/10.1001/archsurg. 137.6.641.
3. Turner JJ, Leotlela PD, Pannett AA, Forbes SA, Bassett JH, Harding B, et al. Frequent occurrence of an intron 4 mutation inmultiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2002;87(6):2688-93, http://dx.doi.org/10.1210/jc.87.6.2688.
4. Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 2008;29(1):22-32, http://dx.doi.org/10.1002/humu.20605.
5. Conte-Devolx B, Niccoli P. Groupe d'étude des Tumeurs Endocrines. Clinical characteristics of multiple endocrine neoplasia. Bull Acad Natl Med. 2010; 194(1):69-78.
6. Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16:363-71, http://dx.doi.org/10.1016/0002-9343(54)90353-8.
7. Khairi MRA, Dexter RN, Burzynski NJ, Johnston CC. Mucosal neuroma, pheochromocytoma and medullary thyroid carcinoma: multiple endocrine neoplasia-type III. Medicine. 1975;54(2):89-112.
8. Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Höfler H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA. 2006; 103: 15558-63. Erratum in: Proc Natl Acad Sci U S A. 2006; 103(50):19213, http://dx.doi.org/10.1073/pnas.0603877103
9. Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, et al. Positional cloning of the gene for multiple endocrine neoplasia type 1. Science. 1997;276(5311):404-7, http://dx.doi.org/10.1126/science.276.5311.404.
10. Lemmens I, van der Ven WJ, Kas K, Zhang CX, Giraud S, Wautot V, et al. Identification of the MEN1 gene. The European consortium on MEN1. Hum Mol Genet. 1997;6(7):1177-83.
11. Zhang HL, Li WY, Zhang CP, Zhu YX, Wu L, Long HM, et al. Differentially expressed genes in Men1 knockout and wild type embryoid bodies for pancreatic islet development. Mol Med Report. 2011;4(2):301-5, http://dx.doi.org/10.3892/mmr.2011.409. Epub 2011 Jan 3.
12. Hughes CM, Rozenblatt-Rosen O, Milne TA, Copeland TD, Levine SS, Lee JC, et al. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Mol Cell. 2004; 13(4):587-97, http://dx.doi.org/10.1016/S1097-2765(04)00081-4.
13. Milne TA, Hughes CM, Lloyd R, Yang Z, Rozenblatt-Rosen O, Dou Y, et al. Menin and MLL cooperatively regulate expression of cyclindependent kinase inhibitors. Proc Natl Acad Sci USA. 2005;102(3):749-54, http://dx.doi.org/10.1073/pnas.0408836102.
14. Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell. 2003;113(7):881-9, http://dx.doi.org/10.1016/S0092-8674(03)00430-6.
15. Dreijerink KM, Höppener JW, Timmers, Lips CJ. Mechanism of disease: MEN 1-relation to chromatin modifications and transcription regulation. Nat Clin Pract Endocr Metab. 2006;2(10):562-70, http://dx.doi.org/10.1038/ncpendmet0292.
16. Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell. 1999;96:143-52, http://dx.doi.org/10.1016/S0092-8674(00)80967-8.
17. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero DJ, Kitabayashi I, et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol. 2004;24(13):5639-49, http://dx.doi.org/10.1128/MCB.24.13.5639-5649.2004.
18. Kim H, Lee JE, Cho EJ, Liu JO, Youn HD. Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex. Cancer Res. 2003;63(19):6135-9.
19. Murai MJ, Chruszcz M, Reddy G, Grembecka J, Cierpicki T. Crystal structure of Menin reveals the binding site for mixed lineage Leukemia (MLL) protein. J Biol Chem. 2011; 9;286(36):31742-8.
20. Yokoyama A, Cleary ML. Menin critically links MLL proteins with LEDGF on cancer-associated target genes. Cancer Cell. 2008;14(1):36-46, http://dx.doi.org/10.1016/j.ccr.2008.05.003.
21. Agarwal SK, Impey S, McWeeney S, Scacheri PC, Collins FS, Goodman RH, et al. Distribution of menin-occupied regions in chromatin specifies a broad role of menin in transcriptional regulation. Neoplasia. 2007;9(2):101-7, http://dx.doi.org/10.1593/neo.06706.
22. Heppner C, Bilimoria KY, Agarwal SK, Kester M, Whitty LJ, Guru SC, et al. The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation. Oncogene. 2001;20(36):4917-25, http://dx.doi.org/10.1038/sj.onc.1204529.
23. Lemmens IH, Forsberg L, Pannett AA, Meyen E, Piehl F, Turner JJ, et al. Menin interacts directly with the homeobox-containing protein Pem. Biochem Biophys Res Commun. 2001;286(2):426-31, http://dx.doi.org/10.1006/bbrc.2001.5405.
24. Kaji H, Canaff L, Lebrun JJ, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling. Proc Natl Acad Sci USA. 2001;98(7):3837-42, http://dx.doi.org/10.1073/pnas.061358098.
25. Shattuck TM, Costa J, Bernstein M, Jensen RT, Chung DC, Arnold A. Mutational analysis of Smad3, a candidate tumor suppressor implicated in TGF-beta and menin pathways, in parathyroid adenomas and enteropancreatic endocrine tumors. J Clin Endocrinol Metab. 2002;87(8):3911-4, http://dx.doi.org/10.1210/jc.87.8.3911.
26. Chen GAJ, Wang M, Farley S, Lee LY, Lee LC, Sawicki MP. Menin promotes the Wnt signaling pathway in pancreatic endocrine cells. Mol Cancer Res. 2008;6(12):1894-907.
27. Dreijerink KM, Mulder KW, Winkler GS, Höppener JW, Lips CJ, Timmers HT. Menin links estrogen receptor activation to histone H3K4 trimethylation. Cancer Res. 2006;66(9):4929-35, http://dx.doi.org/10.1158/0008-5472.CAN-05-4461.
28. Wuescher L, Angevine K, Hinds T, Ramakrishnan S, Najjar SM, Mensah-Osman EJ. Am J Phsyiol Endocrinol Metab. 2011;301(3):E474-83.
29. Sukhodolets KE, Hickman AB, Agarwal SK, Sukhodolets MV, Obungu VH, Novotny EA, et al. The 32-kilodalton subunit of replication protein A interacts with menin, the product of the MEN1 tumor suppressor gene. Mol Cell Biol. 2003;23(2):493-509, http://dx.doi.org/10.1128/MCB.23.2.493-509.2003.
30. Schnepp RW, Hou Z, Wang H, Petersen C, Silva A, Masai H, et al. Functional interaction between tumor suppressor menin and activator of S-phase kinase. Cancer Res. 2004;64(18):6791-6.
31. Busygina V, Kottemann MC, Scott KL, Plon SE, Bale AE. Multiple endocrine neoplasia type 1 interacts with forkhead transcription factor CHES1 in DNA damage response. Cancer Res. 2006;66(17):8397-403, http://dx.doi.org/10.1158/0008-5472.CAN-06-0061.
32. Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, et al. Menin associates with FANCD2, a protein involved in repair of DNA damage. Cancer Res. 2003;63(14):4204-10.
33. Lopez-Egido J, Cunningham J, Berg M, Oberg K, Bongcam-Rudloff E, Gobl A. Menin's interaction with glial fibrillary acidic protein and vimentin suggests a role for the intermediate filament network in regulating menin activity. Exp Cell Res. 2002;278(2):175-83, http://dx.doi.org/10.1006/excr.2002.5575.
34. Wang Y, Ozawa A, Zaman S, Prasad NB, Chandrasekharappa SC, Agarwal SK, et al. The tumor suppressor protein menin inhibits AKT activation by regulating its cellular localization. Cancer Res. 2011;71(2): 371-82, http://dx.doi.org/10.1158/0008-5472.CAN-10-3221.
35. Ohkura N, Kishi M, Tsukada T, Yamaguchi K. Menin, a gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis suppressor nm23. Biochem Biophys Res Commun. 2001;282(5):1206-10, http://dx.doi.org/10.1006/bbrc.2001.4723.
36. Yan J, Yang Y, Zhang H, King C, Kan HM, Cai Y, et al. Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells. Oncogene. 2009;28(7):973-82, http://dx.doi.org/10.1038/onc.2008.435.
37. Obungu VH, Lee Burns A, Agarwal SK, Chandrasekharapa SC, Adelstein RS, Marx SJ. Menin, a tumor suppressor, associates with nonmuscle myosin II-A heavy chain. Oncogene. 2003;22(41):6347-58, http://dx.doi.org/10.1038/sj.onc.1206658.
38. Hou R, Manwaring LP, Moley JF, Whelan AA. A novel missense mutation in the MEN1 gene in a patient with multiple endocrine neoplasia type 1. Endocr Pract. 2011;17(3):e63-7.
39. Vierimaa O, Ebeling TM, Kytölä S, Bloigu R, Eloranta E, Salmi J, et al. Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype phenotype correlation. Eur J Endocrinol. 2007;157(3):285-94, http://dx.doi.org/10.1530/EJE-07-0195.
40. Bazzi W, Renon M, Vercherat C, Hamze Z, Lacheretz-Bernigaud A, Wang H, et al. MEN1 missense mutations impair sensitization to apoptosis induced by wild-type menin in endocrine pancreatic tumor cells. Gastroenterology. 2008;135(5):1698-1709, http://dx.doi.org/10.1053/j.gastro.2008.07.031.
41. Yaguchi H, Ohkura N, Takahashi M, Nagamura Y, Kitabayashi I, Tsukada T. Menin missense mutants associated with multiple endocrine neoplasia type 1 are rapidly degraded via the ubiquitin-proteasome pathway. Mol Cell Biol. 2004;24(15):6569-80, http://dx.doi.org/10.1128/MCB.24.15.6569-6580.2004.
42. Olufemi SE, Green JS, Manickam P, Guru SC, Agarwal SK, Kester MB, et al. Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma variant of MEN1 (MEN1-Burin) in four kindreds from Newfoundland. Hum Mutat. 1998;11(4):264-69, http://dx.doi.org/10.1002/(SICI)1098-1004(1998)11:4,264::AID-HUMU2.3.0.C O;2-V.
43. Kong C, Ellard S, Johnston C, Farid NR. Multiple endocrine neoplasia type 1Burin from Mauritius: a novel MEN1 mutation. J Endocrinol Invest. 2001;24(10):806-10.
44. Hao W, Skarulis MC, Simonds WF, Weinstein LS, Agarwal SK, Mateo C, et al. Multiple endocrine neoplasia type 1 variant with frequent prolactinoma and rare gastrinoma. J Clin Endocrinol Metab. 2004;89(8):3776-84, http://dx.doi.org/10.1210/jc.2003-031511.
45. Agarwal SK, Ozawa A, Mateo CM, Marx SJ. The MEN1 gene and pituitary tumours. Horm Res. 2009;71(Suppl. 2):131-8, http://dx.doi.org/10.1159/000192450.
46. Teh BT, Esapa CT, Houlston R, Grandell U, Farnebo F, Nordenskjöld M, et al. A family with isolated hyperparathyroidism segregating a missense MEN1 mutation and showing loss of the wild-type alleles in the parathyroid tumors. Am J Hum Genet. 1998;63(5):1544-9, http://dx.doi.org/10.1086/302097.
47. Honda M, Tsukada T, Tanaka H, Maruyama K, Yamaguchi K, Obara T, et al. A novel mutation of the MEN1 gene in a Japanese kindred with familial isolated primary hyperparathyroidism. Eur J Endocrinol. 2000;142(2):138-43, http://dx.doi.org/10.1530/eje.0.1420138.
48. Kassem M, Kruse TA, Wong FK, Larsson C, Teh BT. Familial isolated hyperparathyroidism as a variant of multiple endocrine neoplasia type 1 in a large Danish pedigree. J Clin Endocrinol Metab. 2000;85(1):165-7, http://dx.doi.org/10.1210/jc.85.1.165.
49. Miedlich S, Lohmann T, Schneyer U, Lamesch P, Paschke R. Familial isolated primary hyperparathyroidism-a multiple endocrine neoplasia type 1 variant? Eur J Endocrinol. 2001;145(2):155-60, http://dx.doi.org/10.1530/eje.0.1450155.
50. Villablanca A, Wassif WS, Smith T, Höög A, Vierimaa O, Kassem M, et al. Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism. Eur J Endocrinol. 2002;147(3):313-22, http://dx.doi.org/10.1530/eje.0.1470313
51. Simonds WF, James-Newton LA, Agarwal SK, Yang B, Skarulis MC, Hendy GN, et al. Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds. Medicine (Baltimore) 2002;81:1-26.
52. Pannett AA, Kennedy AM, Turner JJ, Forbes SA, Cavaco BM, Bassett JH, et al. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol (Oxf). 2003;58:639-46, http://dx.doi.org/10.1046/j.1365-2265.2003.01765.x.
53. Hannan FM, Nesbit MA, Christie PT, Fratter C, Dudley NE, Sadler GP, Thakker RV. Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene. Nat Clin Pract Endocrinol Metab. 2008;4:53-8, http://dx.doi.org/10.1038/ncpendmet0718.
54. Miyauchi A, Sato M, Matsubara S, Ohye H, Kihara M, Matsusaka K, et al. A family of MEN1 with a novel germline missense mutation and benign polymorphisms. Endocr J. 1998;45:753-9, http://dx.doi.org/10.1507/endocrj.45.753.
55. Ukita C, Yamaguchi M, Tanaka T, Shigeta H, Nishikawa M. A novel missense mutation of the MEN1 gene in a multiple endocrine neoplasia type 1 patient associated with carcinoid syndrome. Intern Med. 2003;42:1112-6, http://dx.doi.org/10.2169/internalmedicine.42.1112.
56. Schaaf L, Pickel J, Zinner K, Hering U, Höfler M, Goretzki PE, et al. Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1. Exp Clin Endocrinol Diabetes. 2007;115:509-17, http://dx.doi.org/10.1055/s-2007-970160.
57. Carrasco CA, González AA, Carvajal CA, Campusano C, Oestreicher E, Arteaga E, et al. Novel intronic mutation of MEN1 gene causing familial isolated primary hyperparathyroidism. J Clin Endocrinol Metab. 2004;89:4124-9, http://dx.doi.org/10.1210/jc.2003-032101.
58. Dreijerink KM, van Beek AP, Lentjes EG, Post JG, van der Luijt RB, Canninga-van Dijk MR, et al. Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease. Eur J Endocrinol. 2005;153:741-6, http://dx.doi.org/10.1530/eje.1.02022.
59. Drori-Herishanu L, Horvath A, Nesterova M, Patronas Y, Lodish M, Bimpaki E, et al. An Intronic mutation is associated with prolactinoma in a young boy, decreased penetrance in his large family, and variable effects on MEN1 mRNA and protein. Horm Metab Res. 2009;41:630-4, http://dx.doi.org/10.1055/s-0029-1216358.
60. Raef H, Zou M, Baitei EY, Al-Rijjal RA, Kaya N, Al-Hamed M, et al. A novel deletion of the MEN1 gene in a large family of multiple endocrine neoplasia type 1 (MEN1) with aggressive phenotype. Clin Endocrinol (Oxf). 2011; May 31, http://dx.doi.org/10.1111/j.1365-2265.
61. Hasani-Ranjbar S, Amoli MM, Ebrahim-Habibi A, Gozashti MH, Khalili N, Sayyahpour FA, et al. A new frameshift MEN1 gene mutation associated with familial malignant insulinomas. Fam Cancer. 2011;10:343-8, http://dx.doi.org/10.1007/s10689-010-9412-z.
62. Stratakis CA, Schussheim DH, Freedman SM, Keil MF, Pack SD, Agarwal SK, et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2000;85:4776-80, http://dx.doi.org/10.1210/jc.85.12.4776.
63. van Wijk JP, Dreijerink KM, Pieterman CR, Lips CJ, Zelissen PM, Valk GD. Increased prevalence of impaired fasting glucose in MEN1 gene mutation carriers. Clin Endocrinol (Oxf). 2011; Jul 4. http://dx.doi.org/10.1111/j.1365-2265.2011.04166.x.
64. Lourenço DM Jr, Toledo RA, Mackowiac II, Coutinho FL, Cavalcanti MG, Correia-Deur JE, et al. MEN1 type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile. Eur J Endocrinol 2008;159:259-74.
65. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92:2017-29, http://dx.doi.org/10.1210/jc.2007-0298.
66. Kayaniyil S, Vieth R, Retnakaran R. Association of vitamin D with insulin resistance an beta cell dysfunction in subjects at risk for diabetes. Diabetes Care 2010;33:1379-81
67. Goudet P, Bonithon-Kopp C, Murat A, Ruszniewski P, Niccoli P, Menegaux F, et al. Gender-related differences in MEN1 lesion occurrence and diagnosis. A 734-case cohort study from the GTE (Groupe d'etude des Tumeurs Endocrines). Eur J Endocrinol. 2011;165:97-105, http://dx.doi.org/10.1530/EJE-10-0950.
68. Karhu A, Aaltonen LA. Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. Hum Mol Genet. 16, spec No 1R73-9. (2007). Hum Mutat. 2002;20:35-47.
69. Georgitsi M, Heliövaara E, Paschke R, Kumar AV, Tischkowitz M, Vierimaa O, et al. Large genomic deletions in AIP in pituitary adenoma predisposition. J Clin Endocrinol Metab. 2008;93:4146-51, http://dx.doi.org/10.1210/jc.2008-1003.
70. Laconi E. The evolving concept of tumor microenvironments. Bioessays. 2007;29:738-44, http://dx.doi.org/10.1002/bies.20606.
71. Dreijerink KM, Varier RA, van Nuland R, Broekhuizen R, Valk GD, van der Wal JE, et al. Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas. Mol Cell Endocrinol. 2009;313:1-8, http://dx.doi.org/10.1016/j.mce.2009.08.020.
72. van Veelen W, van Gasteren CJ, Acton DS, Franklin DS, Berger R, Lips CJ, et al. Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development. Cancer Res. 2008;68:1329-37, http://dx.doi.org/10.1158/0008-5472.CAN-07-5754.
73. Van Veelen W, Klompmaker R, Gloerich M, van Gasteren CJ, van Kalkhoven E, Berger R, et al. P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development. Int J Cancer. 2009;124:339-45, http://dx.doi.org/10.1002/ijc.23977.
74. Agarwal SK, Mateo CM, Marx SJ. Rare germline mutations in cyclindependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states. J Clin Endocrinol Metab. 2009;94:1826-34. Comment in: J Clin Endocrinol Metab. 2009;94:1518-20, http://dx.doi.org/10.1210/jc.2008-2083
75. Owens M, Stals K, Ellard S, Vaidya B. Germline mutations in the CDKN1B gene encoding p27 Kip1 are a rare cause of multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf). 2009;70:499-500, http://dx.doi.org/10.1111/j.1365-2265.2008.03363.x.
76. Igreja S, Chahal HS, Akker SA, Gueorguiev M, Popovic V, Damjanovic S, et al. Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes in multiple endocrine neoplasia (MEN1) syndrome patients without any detectable MEN1 gene mutations. Clin Endocrinol (Oxf). 2009;70:259-64, http://dx.doi.org/10.1111/j.1365-2265.2008.03379.x.
77. Bai F, Pei XH, Nishikawa T, Smith MD, Xiong Y. p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Mol Cell Biol. 2007;27:1495-504, http://dx.doi.org/10.1128/MCB.01764-06.
78. Molatore S, Pellegata NS. The MENX syndrome and p27: relationships with multiple endocrine neoplasia. Prog Brain Res. 2010;182:295-20, http://dx.doi.org/10.1016/S0079-6123(10)82013-8.
79. Marinoni I, Pellegata NS. p27kip1: a new multiple endocrine neoplasia gene? Neuroendocrinology. 2011;93:19-28, http://dx.doi.org/10.1159/000320366.
80. Davenport, Agha A. The role of menin in parathyroid tumorigenesis. Adv Exp Med Biol. 2009;668:79-86, http://dx.doi.org/10.1007/978-1-4419-1664-8_8.
81. Dworakowska D, Grossman AB. The pathophysiology of pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2009;23:525-41, http://dx.doi.org/10.1016/j.beem.2009.05.004.
82. Seoane S, Perez-Fernandez R. The vitamin D receptor represses transcription of the pituitary transcription factor Pit-1 gene without involvement of the retinoid X receptor. Mol Endocrinol. 2006;20:735-48, http://dx.doi.org/10.1210/me.2005-0253.
83. Lacerte A, Lee EH, Reynaud R, Canaff L, de Guise C, Devost D, et al. Activin inhibits pituitary prolactin expression and cell growth through Smads, Pit-1 and menin. Mol Endocr. 2004;18:1558-69, http://dx.doi.org/10.1210/me.2003-0470.
84. Lebrun JJ. Activin, TGF-beta and menin in pituitary tumorigenesis. Adv Exp Med Biol. 2009;668:69-78, http://dx.doi.org/10.1007/978-1-4419-1664-8_7.
85. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011;331:1199-203. Comment in: Science. 2011;331: 1145-6, http://dx.doi.org/10.1126/science.1200609.
86. Ishida E, Yamada M, Horiguchi K, Taguchi R, Ozawa A, Shibusawa N, et al. Attenuated expression of menin and p27 (Kip1) in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor. Endocr J. 2011;58:287-96, http://dx.doi.org/10.1507/endocrj.K10E-158.
87. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006;6:184-92, http://dx.doi.org/10.1038/nrc1819.
88. Pitt SC, Chen H, Kunnimalaiyaan M. Inhibition of phosphatidylinositol 3-kinase/Akt signaling suppresses tumor cell proliferation and neuroendocrine marker expression in GI carcinoid tumors. Ann Surg Oncol. 2009;16:2936-42, http://dx.doi.org/10.1245/s10434-009-0591-5
89. Kim YS, Burns AL, Goldsmith PK, Heppner C, Park SY, Chandrasekharappa SC, et al. Stable overexpression of MEN1 suppresses tumorgenicity of RAS. Oncogene. 1999;18:5936-42, http://dx.doi.org/10.1038/sj.onc.1203005
90. Marx SJ, Simonds WF. Hereditary hormone excess: genes, molecular pathways, and syndromes. Endocr Rev. 2005;26:615-61, http://dx.doi.org/10.1210/er.2003-0037.
91. Goudet P, Murat A, Binquet C, Cardot-Bauters C, Costa A, Ruszniewski P, et al. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d'Etude des Tumeurs Endocrines) cohort study among 758 patients. World J Surg. 2010;34:249-55.
92. The lessons of rare maladies. Annual Oration before the Medical Society of London by Sir Archibald Garrod. Br Med J. 1928:26:914-5.