Abstract
For the past 20 years or so, the multiple endocrine neoplasia (MEN) syndromes have attracted the interest of internists, endocrine surgeons, and pathologists, reflecting both the uniqueness of their clinical and pathologic presentations and the new discovery of important cellular mechanisms responsible for growth, development, and function of several lineages of hormone-secreting cells.
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References
Gardner DG. Recent advances in mutliple endocrine neoplasia syndromes. Adv Int Med 1997; 42: 597–627.
Erdheim, J. Zur normalen und pathologischen Histologie der Glandula thyreoidea, parathyreoidea und Hypophysis. Beitr Pathol Anat 1903; 33: 158–236.
Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med 1954; 16: 363–371.
Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med 1961; 31: 163–166.
Steiner AL, Goodman AD, Powers SR. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism, and Cushing’s disease: multiple endocrine neoplasia type 2. Medicine 1968; 47: 371–409.
Chong GD, Beahrs OH, Sizemore GW, et al. Medullary carcinoma of the thyroid gland. Cancer 1975; 35: 695–704.
Komminoth P. Review: multiple endocrine neoplasia type 1, sporadic neuroendocrine tumors, and menin. Diagn Mol Pathol 1999; 8: 107–112.
DeLellis RA. Multiple endocrine neoplasia syndromes revisited: clinical, morphologic, and molecular features. Lab Invest 1995; 72: 494–505.
Komminoth P, Heitz PU, Klöppel G. Pathology of MEN-1: morphology, clinicopathologic correlations and tumor development. J Intern Med 1998; 243: 455–464.
Carty SE, Helm AK, Amico JA, et al. The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1. Surgery 1998; 124: 1106–1113.
Wilkinson S, Teh BT, Davey KR, McArdle JP, Young M, Shepherd JJ. Cause of death in multiple endocrine neoplasia type 1. Arch Surg 1993; 128: 683–690.
DeLellis RA. Tumors of the parathyroid gland. Atlas of Tumor Pathology (Third Series, Fasicle 6). Washington, DC: Armed Forces Institute of Pathology, 1991; 26: 65–68.
Arnold A. Parathyroid adenomas: clonality in benign neoplasia. In: Crossman J, ed. Molecular Genetics in Cancer Diagnosis. New York: Elsevier, 1990: 399–408.
Friedman E, Sakaguchi K, Bale AE, et al. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type I. N Engl J Med 1989; 321: 213–218.
Mallette LE. Management of hyperparathyroidism in the multiple endocrine neoplasia syndromes and other familial endocrinopathies. Endocrinol Metab Clin N Am 1994; 23: 19–36.
Proye C, Carnaille B, Quievreux JL, Combemale F, Oudar C, Lecomte-Houcke M. Late outcome of 304 consecutive patients with multiple gland enlargement in primary hyperparathyroidism treated by conservative surgery. World J Surg 1998; 22: 526–530.
Tsutsumi Y. Pathology of multiple pancreatic endocrine tumors. Pathol Clin Med (Rinsho to Byori) 1984; 2: 452–466 (in Japanese).
Klöppel G, Willemer S, Stamm B, Häcki WH, Heitz PU. Pancreatic lesion and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type1. An immunohistochemical study of nine patients. Cancer 1986; 57: 1824–1832.
Kameya T. Pathology of islet cell tumors. In: Nakamura T, Sasano N, Kuroda S, eds. Islet Cell Tumor. Tokyo: Igaku-Tosho-Schuppan, 1983: 11–21 (in Japanese).
Pipeleers-Marichal M, Somers G, Willems G, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger–Ellison syndrome. N Engl J Med 1990; 322: 723–737.
Croisier JC, Azérad E, Lubetzki J. L’adenomatose polyendocrinienne (syndrome de Wermer). A propos d’une observation personelle. Revue de la littérature. Sem Hôp Paris 1971; 47: 495–525.
Capella C, Riva C, Rindi G, et al. Histopathology, hormone products, and clinicopathological profile of endocrine tumors of the upper small intestine; a study of 44 cases. Endocr Pathol 1991; 2: 92v110.
LeBodic MF, Heymann MF, Lecomte M, Berger N, et al. Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple-endocrine neoplasia type I. Am J Surg Pathol 1996; 20: 1378–1384.
MacFarlane MP, Fraker D, Alexander HR, Norton JA, Lubensky I, Jensen RT. Prospective study of surgical resction of duodenal and pancreatic gastrinomas in multiple endocrine neoplasia type 1. Surgery 1995; 118: 973–980.
Thompson NW, Pasieka J, Fukuuchi A. Duodenal gastrinomas, duodenotomy, and duodenal exploration in the surgical management of Zollinger–Ellison syndrome. World J Surg 1993; 17: 455–462.
Thompson NW, Vinik AI, Eckhauser FE. Microgastrinomas of the duodenum. Ann Surg 1989; 209: 396–404.
Pipeleers-Marichal M, Donow C, Heitz P, Klöppel G. Pathologic aspects of gastrinomas in patients with Zollinger–Ellison syndrome with and without multiple endocrine neoplasia type I. World J Surg 1993; 17: 481–488.
Scheithauer BW, Laws ER, Kovacs K, Horvath E, Randall RV, Ryan N. Plurihormonal pituitary adenomas. Sem Diagn Pathol 1987; 4: 205–211.
Oberg K, Skogseid B, Eriksson B. Multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical and genetic investigations. Acta Oncol 1989; 28: 383–387.
Capella C, Riva C, Leutner M, La Rosa S. Pituitary lesion in multiple endocrine neoplasia syndrome (MENS) type 1. Pathol Res Pract 1995; 191: 345–347.
Komminoth P. Multiple endocrine neoplasia type 1 and 2: from morphology to molecular pathology. Verh Dtsch Ges Pathol 1997; 81: 125–138.
Trump D, Farren B, Wooding C, Pang JT, Besser GM, Buchanan KD. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 1996; 89: 653–669.
Anderson RJ, Lufkin EG, Sizemore GW, Carney JA, Sheps SG, Silliman YE. Acromegaly and pituitary adenoma with pheochromocytoma: a variant of multiple endocrine neoplasia. Clin Endocrinol 1981; 14: 605–612.
Padberg B, Schröder S, Capella C, Frilling A, Klöppel G, Heitz PU. Multiple endocrine neoplasia type 1 (MEN-1) revisited. Virchows Arch 1995; 426: 541–548.
Thakker RV, Ponder BAJ. Multiple endocrine neoplasia. Baillieres Clin Endocrinol Metab 1988; 2: 1031–1067.
Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M. Multiple facial angioifbromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol 1997; 133: 853–857.
Thakker R. Editorial: Multiple endocrine neoplasia–syndromes of the twentieth century. J Clin Endocr Metab 1998; 83: 2617–2619.
Calender A. Genetic testing in multiple endocrine neoplasia and related syndromes. Forum 1998;8. 2: 146–159.
Learoyd DL, Delbridge LW, Robinson BG. Multiple endocrine neoplasia. Aust NZ J Med 2000; 30: 675–681.
Phay J, Moley JF, Lairmore TC. Multiple endocrine neoplasias. Semin Surg Oncol 2000; 18: 324–332.
Moers AM, Landsrater RM, Schaap C, et al. Familial medullary thyroid carcinoma: not a distinct entity? Genotype–phenotype correlation in a large family. Am J Med 1996; 101: 635–641.
Raue F, Frank-Raue K, Grauer A. Multiple endocrine neoplasia type 2. Clinical features and secreening. Endocrinol Metab Clin North Am 1994; 23: 137–156.
Snow KH, Boy A. Management of individual tumor syndromes. Medullary thyroid carcinoma and hyperparathyroidism. Endocrinol Metab Clin North Am 1994; 23: 157–166.
Wells SA, Chi DD, Toshima K, et al. Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A. Ann Surg 1994; 200: 237–250.
Guyétant S, Rousselet M-C, Durigon M, et al. Sex related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J Clin Endocrinol Metab 1997; 82: 42–47.
Albores-Saavedra J, Kreuger JE. C-cell hyperplasia and medullary carcinoma. Endocr Pathol 2001; 12: 365–377.
McDermott MB, Swanson PE, Wick MR. Immunostains for collagen type IV discriminate between C-cell hyperplasia and microscopic medullary carcinoma in multiple endocrine neoplasia, type 2a. Hum Pathol 1995; 26: 1308–1312.
Gallagher LA, Pilch B2, Gaz RD, et al. Histologic and clinicopathologic features of 31 medullary microcarcinomas and their precursors. Mod Pathol 2110; 14: 433.
Kaserer K, Scheuba C, Neuhold N, et al. Sporadic versus familial medullary thyroid microcarcinoma. A histopathologic study of 50 consecutive cases. Am J Surg Pathol 2001; 25: 1245–1251.
Saad MF, Ordonez NG, Rashid RK, Guido JJ, Hill CS, Hicky RC, Samaan NA. Medullary carcinoma of the thyroid: a study of the clinical features and prognostic factors in 161 patients. Medicine 1984; 63: 319–342.
Bigner SH, Cox EB, Mendelsohn G, Baylin SB, Wells SA Jr, Eggleston JC. Medullary carcinoma of the thyroid in the multiple endocrine neoplasia IIA syndrome. Am J Surg Pathol 1981; 5: 459–472.
Norton JA, Froome LC, Farrell RE, Wells SA J. Multiple endocrine neoplasia type IIb; the most aggressive form of medullary thyroid carcinoma. Surg Clin North Am 1979; 59: 109–118.
Baloch ZE, LiVolsi VA. Prognostic factors in well differentiated follicular-derived carcinoma and medullary thyroid carcinoma. Thyroid 2001; 11: 637–645.
Iwashita T, Asai N, Murakami H, Matsuyama M, Takahashi M. Identiifcation of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN 2A or MEN 2B mutation. Oncogene 1996; 12: 481–487.
Lack EE. Tumors of the adrenal gland and extra-adrenal paraganglia (Third Series, Fascicle 19). Washington, DC: Armed Forces Institute of Pathology, 1997: 243–246.
Glushien AS, Mansuy MM, Littman DS. Pheochromocytoma:its relationship to the neuroeutaneous syndromes. Am J Med 1953; 14: 318–327.
Neuman HP, Berger DP, Sigmund G, et al. Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel–Lindau disease. N Engl J Med 1993; 329: 1531–1538.
Chetty R, Duhig JD. Bilateral pheochromocytomas-ganglioneuroma of the adrenal in type 1 neurofibromatosis. Am J Surg Pathol 1993; 17: 837–841.
Evans DB, Lee JE, Merell RC, Hickey RC. Adrenal medullary disease in multiple endocrine neoplasia type 2. Appropriate management. Endocrinol Metab Clin North Am 1993; 23: 167–176.
Cance WG, Wells SA Jr. Multiple endocrine neoplasia type IIa. Curr Prob Surg 1985; 22: 7–56.
Gagel RF, Tashjian AH Jr, Cummings T, et al. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N Engl J Med 1988; 318: 478–484.
DeLellis RA, Wolfe HJ, Gagel RT, et al. Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma. Am J Pathol 1976; 83: 177–190.
Caron P, Attie T, David D, et al. C618 mutation in exon 10 of the RET protooncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung’s disease. J Clin Endocrinol Metab 1996; 81: 2731–2733.
Demos TC, Blonder J, Shey WL, Braithwaite SS, Goldstein PL. Multiple endocrine neoplasia (MEN) syndrome type IIB; gastrointestinal manifestations. Am J Roentgenol 1983; 140: 73–78.
Chappuis-Flament S, Pasini A, De Vita G, et al. Dual effect on the RET receptor of MEN 2 mutations affecting speciifc extracytoplasmic cysteines. Oncogene 1998; 17: 2851–2861.
Chandrasekharappa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997; 276: 404–407.
The European Consortium on MEN1. Identiifcation of the multiple endocrine neoplasia type 1 (MEN1) gene. Hum Mol Genet 1997; 6: 1177–1183.
Bassett JHD, Rashbass P, Harding B, Forbes SA, Pannett AAJ, Thakker RV. Studies of the murine homolog of the multiple endocrine neoplasia type 1 (MEN1) gene, men1. J Bone Miner Res 1999; 14: 3–10.
Ikeo Y, Sakurai A, Suzuki R, et al. Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage. Lab Invest 2000; 80: 797–804.
Karges W, Maier S, Wissmann A, Dralle H, Dosch HM, Boehm BO. Primary structure, gene expression and chromosomal mapping of rodent homologs of the MEN1 tumor suppressor gene. Biochim Biophys Acta 1999; 1446: 286–294.
Maruyama K, Tsukada T, Hosono T, et al. Structure and distribution of rat menin mRNA. Mol Cell Endocrinol 1999; 156: 25–33.
Stewart C, Parente F, Piehl F, et al. Characterization of the mouse Men1 gene and its expression during development. Oncogene 1998; 17: 2485–2493.
Wautot V, Khodaei S, Frappart L, et al. Expression analysis of endogenous menin, the product of the multiple endocrine neoplasia type 1 gene, in cell lines and human tissues. Int J Cancer 2000; 85: 877–881.
Khodaei S, O’Brien KP, Dumanski J, Wong FK, Weber G. Characterization of the MEN1 ortholog in zebraifsh. Biochem Biophys Res Commun 1999; 264: 404–408.
Manickam P, Vogel AM, Agarwal SK, et al. Isolation, characterization, expression and functional analysis of the zebraifsh ortholog of MEN1. Mamm Genome 2000; 11: 448–454.
Maruyama K, Tsukada T, Honda M, et al. Complementary DNA structure and genomic organization of drosophila menin. Mol Cell Endocrinol 2000; 168: 135–140.
Rubin GM, Yandell MD, Wortman JR, et al. Comparative genomics of the eukaryotes. Science 2000; 287: 2204–2215.
van Kesteren RE, Syed NI, Munno DW, et al. Synapse formation between central nervous neurons requires postsynaptic expression of the MEN1 tumor suppressor gene. J Neurosci 2001;21:RC161 (1-5).
Tsukada T, Yamaguchi K, Kameya T. The MEN1 gene and associated diseases: an update. Endocr Pathol 2001; 12: 259–273.
Agarwal SK, Kester MB, Debelenko LV, et al. Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 1997; 6: 1169–1175.
Shimizu S, Tsukada T, Futami H, et al. Germline mutations of the MEN1 gene in Japanese kindred with multiple endocrine neoplasia type 1. Jpn J Cancer Res 1997; 88: 1029–1032.
Bassett JHD, Forbes SA, Pannett AAJ, et al. Characterization of mutations in patients with multiple endocrine neoplasia type 1. Am J Hum Genet 1998; 62: 232–244.
Giraud S, Zhang CX, Serova-Sinilnikova O, et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 1998; 63: 455–467.
Knudson AG. Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol 1996; 122: 135–140.
Crabtree JS, Scacheri PC, Ward JM, et al. A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc Natl Acad Sci USA 2001; 98: 1118–1123.
Guru SC, Goldsmith PK, Burns AL, et al. Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA 1998; 95: 1630–1634.
Huang SC, Zhuang Z, Weil RJ, et al. Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin. Lab Invest 1999; 79: 301–310.
Agarwal SK, Guru SC, Heppner C, et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 1999; 96: 143–152.
Gobl AE, Berg M, Lopez-Egido JR, Öberg K, Skogseid B, Westin G. Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism. Biochim Biophys Acta 1999; 1447: 51–56.
Knapp JI, Heppner C, Hickman AB, et al. Identiifcation and characterization of JunD missense mutants that lack menin binding. Oncogene 2000; 19: 4706–4712.
Heppner C, Bilimoria KY, Agarwal SK, et al. The tumor suppressor protein menin interacts with NF-xB proteins and inhibits NF-xBmediated transactivation. Oncogene 2001; 20: 4917–4925.
Kaji H, Canaff L, Lebrun J-J, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein blocks transforming growth factor type-b-signaling. Proc Natl Acad Sci USA 2001;98:3837– 3842.
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. Biochm Biophy Res Commun 2001; 282: 1206–1210.
Lemmens IH, Forsberg L, Pannett AAJ, et al. Menin interacts directly with homeobox-containing protein Pem. Biochem Biophys Res Commun 2001; 286: 426–431.
Morelli A, Falchetti A, Martineti V, et al. MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1. Eur J Endocrinol 2000; 142: 131–137.
Kishi M, Tsukada T, Shimizu S, et al. A novel splicing mutation (894-9 G -4 A) of the MEN1 gene responsible for multiple endocrine neoplasia type 1. Cancer Lett 1999; 142: 105–110.
Kishi M, Tsukada T, Shimizu S, et al. A large germline deletion of the MEN1 gene in a family with multiple endocrine neoplasia type 1. Jpn J Cancer Res 1998; 89: 1–5.
Bergman L, Teh B, Cardinal J, et al. Identification of MEN1 gene mutations in families with MEN 1 and related disorders. Br J Cancer 2000; 83: 1009–1014.
Stock JL, Warth MR, Teh BT, et al. A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus at chromosome region 11q13. J Clin Endocrinol Metab 1997; 82: 486–492.
Hai N, Aoki N, Shimatsu A, Mori T, Kosugi S. Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: analysis of 20 Japanese sporadic cases with MEN1. Clin Endocrinol (Oxf) 2000; 52: 509–518.
Karges W, Jostarndt K, Maier S, et al. Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region. J Endocrinol 2000; 166: 1–9.
Fujimori M, Shirahama S, Sakurai A, et al. Novel V184E MEN1 germline mutation in a Japanese kindred with familial hyperparathyroidism. Am J Med Genet 1998; 80: 221–222.
Teh BT, Esapa CT, Houlston R, 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: 1544–1549.
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: 165–167.
Poncin J, Abs R, Velkeniers B, Bonduelle M, et al. Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. Hum Mutat 1999; 13: 54–60.
Honda M, Tsukada T, Tanaka H, et al. A novel mutation of the MEN1 gene in a Japanese kindred with familial isolated primary hyperparathyroidism. Eur J Endocrinol 2000; 142: 138–143.
Miedlich S, Lohmann T, Lamesch P, Paschke R. Familial isolated primary hyperparathyroidism—a multiple endocrine neoplasia type 1 variant? Eur J Endocrinol 2001; 145: 155–160.
Ohye H, Sato M, Matsubara S, et al. Germline mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in a family with primary hyperparathyroidism. Endocr J 1998; 45: 719–723.
Uchino S, Noguchi S, Sato M, et al. Screening of the MEN1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors. Cancer Res 2000; 60: 5553–5557.
Sato M, Miyauchi A, Namihira H, et al. A newly recognized germ-line mutation of MEN1 gene identiifed in a patient with parathyroid adenoma and carcinoma. Endocrine 2000; 12: 223–226.
Görtz B, Roth J, Speel EJM, et al. MEN1 gene mutation analysis of sporadic adrenocortical lesions. Int J Cancer 1999; 80: 373–379.
Fujii T, Kawai T, Saito K, et al. MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation. Pathol Int 1999; 49: 968–973.
Görtz B, Roth J, Krähenmann A, et al. Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol 1999; 154: 429–436.
Mayr B, Apenberg S, Rothämel T, von zur Mühlen A, Brabant G. Menin mutations in patients with multiple endocrine neoplasia type 1. Eur J Endocrinol 1997; 137: 684–687.
Tanaka C, Yoshimoto K, Yamada S, et al. Absence of germ-line mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in familial pituitary adenoma in contrast to MEN1 in Japanese. J Clin Endocrinol Metab 1998; 83: 960–965.
Teh BT, Kytölä S, Farnebo F, et al. Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism. J Clin Endocrinol Metab 1998; 83: 2621–2626.
Gadelha MR, Prezant TR, Une KN, et al. Loss of heterozygosity on chromosome 1 1q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene. J Clin Endocrinol Metab 1999; 84: 249–256.
Ackermann F, Krohn K, Windgassen M, Buchfelder M, Fahlbusch R, Paschke R. Acromegaly in a family without a mutation in the menin gene. Exp Clin Endocrinol Diabetes 1999; 107: 93–96.
Agarwal SK, Debelenko LV, Kester MB, et al. Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. Hum Mutat 1998; 12: 75–82.
Emmert-Buck MR, Debelenko LV, Agarwal S, et al. 1 1q13 allelotype analysis in 27 Northern American MEN1 kindreds identifies two distinct founder chromosomes. Mol Genet Metab 1998; 63: 151–155.
Bear JC, Briones-Urbina R, Fahey JF, Farid NR. Variant multiple endocrine neoplasia I (MEN IBurin): further studies and non-linkage to HLA. Hum Hered 1985; 35: 15–20.
Olufemi S-E, Green JS, Manickam P, et al. Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma variant of MEN1 (MEN1Burin) in four kindreds from Newfoundland. Hum Mutat 1998; 11: 264–269.
Kong C, Ellard S, Johnston C, Farid NR. Multiple endocrine neoplasia type 1Burin from Mauritius: a novel MEN1 mutation. J Endocrinol Invest 2001; 24: 806–810.
Abe T, Yoshimoto K, Taniyama M, et al. An unusual kindred of the multiple endocrine neoplasia type 1 (MEN1) in Japanese. J Clin Endocrinol Metab 2000; 85: 1327–1330.
Veldhuis JD, Norton JA, Wells SA Jr, Vinik AI, Perry RR. Surgical versus medical management of multiple endocrine neoplasia (MEN) type I. J Clin Endocrinol Metab 1997; 82: 357–364.
Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001; 86: 5658–5671.
Beaudet AL, Tsui L-C. A suggested nomenclature for designating mutations. Hum Mutat 1993; 2: 245–248.
Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret by DNA rearrangement. Cell 1985; 42: 581–588.
Pasini B, Hofstra RM, Yin L, et al. The physical map of the human RET proto-oncogene. Oncogene 1995; 11: 1737–1743.
Myers SM, Eng C, Ponder BAJ, et al. Characterization of RET proto-oncogene 3’ splicing variants and polyadenylation sites: a novel C-terminal for RET. Oncogene 1995; 11: 2039–2045.
Takahashi MCooper GM. Ret transforming gene encodes a fusion protein homologous to tyrosine kinases. Mol Cell Biol 1987;7:1378– 1385.
Takahashi M, Buma Y, Iwamoto T, et al. Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene 1988; 3: 571–578.
Lairmore TC, Dou S, Howe JR, et al. A 1.5-megabase yeast artiifcial chromosome contig from human chromosome 10q1 1.2 connecting three genetic loci (RE T, D10S94, and D10S102) closely linked to the MEN2A locus. Proc Natl Acad Sci USA 1993; 90: 492–496.
Mole SE, Mulligan LM, Healey CS, et al. Localisation of the gene for multiple endocrine neoplasia type 2A to a 480 kb region in chromosome band 10q1 1.2. Hum Mol Genet 1993; 2: 247–252.
Pachnis V, Mankoo B, Costantini F. Expression of the c-ret proto-oncogene during mouse embryogenesis. Development 1993; 119: 1005–1017.
Schuchardt A, D’Agati V, Larsson-Blomberg L, et al. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 1994; 367: 380–383.
Trupp M, Arenas E, Fainzilber M, et al. Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 1996; 381: 785–789.
Durbec P, Marcos-Gutierrez CV, Kilkenny C, et al. GDNF signalling through the Ret receptor tyrosine kinase. Nature 1996; 381: 789–793.
Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 1996; 384: 467–470.
Baloh RH, Tansey MG, Lampe PA, et al. Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex. Neuron 1998; 21: 1291–1302.
Milbrandt J, de Sauvage FJ, Fahrner TJ, et al. Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 1998; 20: 245–253.
Airaksinen MS, Titievsky ASaarma M. GDNF family neurotrophic factor signaling: four masters, one servant? Mol Cell Neurosci 1999; 13: 313–325.
Mulligan LM, Marsh DJ, Robinson BG, et al. Genotype–phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium. J Intern Med 1995;238:343– 346.
Eng C, Clayton D, Schuffenecker I, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 1996; 276: 1575–1579.
Eng C, Mulligan LM, Smith DP, et al. Mutation of the RET protooncogene in sporadic medullary thyroid carcinoma. Genes Chromosomes Cancer 1995; 12: 209–212.
Bolino A, Schuffenecker I, Luo Y, et al. RET mutations in exons 13 and 14 of FMTC patients. Oncogene 1995; 10: 2415–2419.
Hoppner W, Ritter MM. A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2A. Hum Mol Genet 1997; 6: 587–590.
Berndt I, Reuter M, Saller B, et al. A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A. J Clin Endocrinol Metab 1998; 83: 770–774.
Hofstra RM, Fattoruso O, Quadro L, et al. A novel point mutation in the intracellular domain of the ret protooncogene in a family with medullary thyroid carcinoma. J Clin Endocrinol Metab 1997; 82: 4176–4178.
Gimm O, Marsh DJ, Andrew SD, et al. Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation. J Clin Endocrinol Metab 1997; 82: 3902–3904.
Eng C, Smith DP, Mulligan LM, et al. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Hum Mol Genet 1994; 3: 237–241.
Marsh DJ, Learoyd DL, Andrew SD, et al. Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma. Clin Endocrinol 1996; 44: 249–257.
Romei C, Elisei R, Pinchera A, et al. Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence. J Clin Endocrinol Metab 1996; 81: 1619–1622.
Komminoth P, Kunz E, Hiort O, et al. Detection of RET proto-oncogene point mutations in paraffin-embedded pheochromocytoma specimens by nonradioactive single-strand conformation polymorphism analysis and direct sequencing. Am J Pathol 1994; 145: 922–929.
Beldjord C, Desclaux-Arramond F, Rafifn-Sanson M, et al. The RET protooncogene in sporadic pheochromocytomas: frequent MEN 2-like mutations and new molecular defects. J Clin Endocrinol Metab 1995;80:2063-2068.
Lindor NM, Honchel R, Khosla S, et al. Mutations in the RET protooncogene in sporadic pheochromocytomas. J Clin Endocrinol Metab 1995; 80: 627–629.
Skinner MA, DeBenedetti MK, Moley JF, et al. Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg 1996; 31: 177–181.
Lips CJ, Landsvater RM, Hoppener JW, et al. Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 1994; 331: 828–835.
Lips CJ. Clinical management of the multiple endocrine neoplasia syndromes: results of a computerized opinion poll at the Sixth International Workshop on Multiple Endocrine Neoplasia and von Hippel– Lindau Disease. J Intern Med 1998; 243: 589–594.
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Kameya, T., Tsukada, T., Futami, H., Yamaguchi, K. (2004). Multiple Endocrine Neoplasia. In: Lloyd, R.V. (eds) Endocrine Pathology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-403-0_19
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DOI: https://doi.org/10.1007/978-1-59259-403-0_19
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