Through insights into the molecular genetics of neuroendocrine tumors (NETs), the genes predisposing to multiple endocrine neoplasia (MEN) syndromes were identified. In MEN1, tumors occur in the parathyroids, endocrine pancreas, anterior pituitary, adrenal glands and thymic neuroendocrine tissues. The MEN1 gene encodes a putative growth-suppressor protein, menin, binding JunD, a transcriptional factor belonging to the AP-1 complex. However, new partners binding menin remain to be found. The MEN1 gene might be involved in 1–50% of sporadic NETs. Another critical mechanism involved in NETs is the deregulation of the RET-signalling pathways by oncogenic point mutations responsible for MEN2 syndromes. MEN2 refers to the inherited forms of medullary thyroid carcinoma. The RET proto-oncogene, a tyrosine-kinase receptor, is activated by missense mutations occurring either in the extracellular dimerization domain or intracellular tyrosine kinase catalytic regions. In both cases the receptor is constitutionally activated in the absence of natural ligands. Endocrine tumors also belong to the clinical pattern of Recklinghausen (NF1) and von Hippel-Lindau (VHL) diseases. The genes for both syndromes have been characterized and provide new pathways for endocrine tumorigenesis related to G-protein physiology (NF1) and transcriptional regulation and/or endothelial cell proliferation (VHL), respectively. Here, we propose a basic overview of recent data on genetic events leading a normal endocrine cell towards a fully malignant phenotype.

1.
Wermer P: Genetic aspects of adenomatosis of endocrine glands. Am J Med 1954;16:363–371.
2.
Sheperd JJ: The natural history of multiple endocrine neoplasia type 1: Highly uncommon or highly unrecognized? Arch Surg 1991;126:935–952.
[PubMed]
3.
Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M: Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol 1997;133:853–857.
[PubMed]
4.
Kato H, Uchimura I, Morohoshi M, Fujisawa K, Kobayashi Y, Numano F, Goseki N, Endo M, Tamura A, Nagashima C: Multiple endocrine neoplasia type 1 associated with spinal ependymoma. Jpn Intern Med 1996;35:285–289.
5.
Giraud S, Choplin H, Teh BT, Lespinasse J, Jouvet A, Labat-Moleur F, Lenoir GM, Calender A: A large multiple endocrine neoplasia type 1 family with clinical expression suggestive of anticipation. J Clin Endocrinol Metab 1997;82:3487–3492.
[PubMed]
6.
Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjöld M: Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 1988;332:85–87.
[PubMed]
7.
Bystrom C, Larsson C, Blomberg C, Sandelin K, Falkmer U, Skogseid B, Oberg K, Werner S, Nordenskjold M: Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. Proc Natl Acad Sci USA 1990;87:1968–1972.
[PubMed]
8.
Knudson AG Jr: Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68:820–823.
[PubMed]
9.
Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang ZP, 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, Lee Burns A, Marx SJ: Positional cloning of the gene for multiple endocrine neoplasia type 1. Science 1997;276:404–407.
[PubMed]
10.
European Consortium on MEN1: Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. Hum Mol Genet 1997;6:1177–1183.
[PubMed]
11.
Guru SC, Goldsmith PK, Burns AL, Marx SJ, Spiegel AM, Collins FS, Chandrasekharappa SC: Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA 1998;95:1630–1634.
[PubMed]
12.
Huang SC, Zhuang Z, Weil RJ, Pack S, Wang C, Krutzsch HC, Pham TA, Lubensky IA: Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin. Lab Invest 1999;79:301–310.
[PubMed]
13.
Kaji H, Canaff L, Goltzmann D, Hendy GN: Cell cycle regulation of menin expression. Cancer Res 1999;59:5097–5101.
[PubMed]
14.
Stewart C, Parente F, Piehl F, Farnebo F, Quincey D, Silins G, Bergman L, Carle GF, Lemmens I, Grimmond S, Xian CZ, Khodei S, Teh B, Lagercrantz J, Siggers P, Calender A, Van de Vem V, Kas K, Weber G, Hayward N, Gaudray P, Larsson C: Characterization of the mouse MEN1 gene and its expression during development. Oncogene 1998;17:2485–2493.
[PubMed]
15.
Bassett JH, Rashbass P, Harding B, Forbes SA, Pannett AA, 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.
16.
Karges W, Maier S, Wissmann A, Dralle H, Dosch HM, Boehm BO: Primary structure, gene expression and chromosomal mapping of rodents homologs of the MEN1 tumor suppressor gene. Biochim Biophys Acta 1999;1446:286–294.
[PubMed]
17.
Maruyama K, Tsukada T, Hosono T, Ohkura N, Kishi M, Honda M, Nara-Ashizawa N, Nagasaki K, Yamaguchi K: Structure and distribution of rat menin mRNA. Mol Cell Endocrinol 1999;156:25–33.
[PubMed]
18.
Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL: Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 1999;96:143–152.
[PubMed]
19.
Gobl AE, Berg M, Lopez-Egido JR, Oberg K, Skogseid B, Westin G: Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism. Biochim Biophys Acta 1999;1447:51–56.
[PubMed]
20.
Karim M, Liu Z, Zandi E: AP1 function and regulation. Curr Opin Cell Biol 1997;9:240–246.
[PubMed]
21.
Kim YS, Burns L, Goldsmith PK, Heppner C, Park SY, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ: Stable overexpression of MEN1 suppresses tumorigenicity of RAS. Oncogene 1999;21:5936–5942.
22.
Agarwal S, Kester MB, Debelenko LV, Heppner C, Emmert-Buck MR, Skarulis M, Doppman J, Kim Y, Lubensky IA, Zhuang ZP, Boguski MS, Weisemann J, Green J, Guru SC, Manickam P, Olufemi SE, Liotta LA, Chandrasekharappa SC, Collins FS, Spiegel AM, Burns AL, Marx SJ: Germline mutations of the MEN1 gene in familial MEN1 and related states. Hum Mol Genet 1997;6:1169–1175.
[PubMed]
23.
Shimizu S, Tsukada T, Futami H, Ui K, Kameya T, Kawanaka M, Uchiyama S, Shimizu S, Tsukada T, Futami H, Ui K, Kameya T, Kawanaka M, Uchiyama S, Aoki A, Yasuda H, Kawano S, Ito Y, Kanbe M, Obara T, Yamaguchi K: Germline mutations of the MEN1 gene in Japanese kindreds with multiple endocrine neoplasia type 1. Jpn J Cancer 1997;88:1029–1032.
24.
Bassett JHD, Forbes SA, Pannett AAJ, Lloyd SE, Christie PT, Wooding C, Harding B, Besser GM, Edwards CR, Monson JP, Sampson J, Wass JA, Wheeler MH, Thakker RV: Characterization of mutations in patients with multiple endocrine neoplasia type 1. Am J Hum Genet 1998;62:232–244.
[PubMed]
25.
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 GM, Gaudray P, Proye C, Conte-Devolx B, Chanson P, Shugart YY, Goldgar D, Murat A, Calender A: Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 1998;63:455–467.
[PubMed]
26.
Teh BT, Kytöla S, Farnebo F, Bergman L, Wong FK, Weber G, Hayward NK, 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, Larsson C: 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.
[PubMed]
27.
Poncin J, Abs R, Velkeniers B, Bonduelle M, Abramowicz M, Legros JJ, Verloes A, Meurisse M, Van Gaal L, Verellen C, Koulischer L, Beckers A: Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. Hum Mutat 1999;13:54–60.
[PubMed]
28.
Mutch MG, Dilley WG, Sanjurjo F, DeBenedetti MK, Doherty GM, Wells SA Jr, Goodfellow PJ, Lairmore TC: Germline mutations in the multiple endocrine neoplasia type 1 gene: Evidence for frequent splicing defects. Hum Mutat 1999;13:175–185.
[PubMed]
29.
Kishi M, Tsukada T, Shimizu S, Hosono K, Ohkubo T, Kosuge T, Sugano K, Kanbe M, Obara T, Yamaguchi K: A novel splicing (894-9 G>A) of the MEN1 gene responsible for multiple endocrine neoplasia type 1. Cancer Lett 1999;142:105–110.
[PubMed]
30.
European Consortium on MEN1: Linkage disequilibrium studies in multiple endocrine neoplasia type 1 (MEN1). Hum Genet 1997;100:657–665.
[PubMed]
31.
Agarwal SK, Debelenko LV, Kester MB, Guru SC, Manickam P, Olufemi SE, Skarulis MC, Heppner C, Crabtree JS, Lubensky IA, Zhuang Z, Kim YS, Chandrasekharappa SC, Collins FS, Liotta LA, Spiegel AM, Burns AL, Emmert-Buck MR, Marx SJ: Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. Hum Mutat 1998;12:75–82.
[PubMed]
32.
Emmert-Buck MR, Debelenko LV, Agarwal S, Kester MB, Manickam P, Zhuang Z, Guru SC, Olufemi SE, Burns AL, Chandrasekharappa SC, Lubensky IA, Liotta LA, Skarulis MC, Spiegel AM, Marx SJ, Collins FS: 11q13 alleotype analysis in 27 northern American MEN1 kindreds identifies two distinct founder chromosomes. Mol Genet Metab 1998;63:151–155.
[PubMed]
33.
Olufemi SE, Green JS, Mannickam 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.
[PubMed]
34.
Weitzmann MN, Woodford KJ, Usdin K: DNA secondary structures and the evolution of hypervariable tandem arrays. J Biol Chem 1997;272:9517–9523.
[PubMed]
35.
Fujimori M, Shirahama S, Sakurai A, Hashizume K, Hama Y, Ito K, Shingu K, Kobayashi S, Amano J, Fukushima Y: Novel V184E MEN1 germline mutation in a Japanese kindred with familial hyperparathyroidism. Am J Med Genet 1998;80:221–222.
[PubMed]
36.
Kassem M, Kruse TA, Wong FK, Larsson C, Teh BT: Familial isolated hyperparathyroidism a variant of multiple endocrine neoplasia type 1 in a Danish pedigree. J Clin Endocrinol Metab 2000;85:165–167.
[PubMed]
37.
Calender A: New insights in genetics of digestive neuroendocrine tumors; in Mignon M, Colombel JF (eds): Recent Advances in the Pathophysiology and Management of Inflammatory Bowel Diseases and Digestive Endocrine Tumors. EAGE, Postgraduate Course. Montrouge, John Libbey Eurotext, 1999, pp 155–172.
38.
Wautot V, Khodaei S, Frappart L, Buisson N, Baro E, Lenoir GM, Calender A, Zhang CX, Weber G: 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.
[PubMed]
39.
Farnebo F, Teh BT, Kytola S, Svensson A, Phelan C, Sandelin K, Thompson NW, Hoog A, Weber G, Farnebo LO, Larsson C: Alterations of the MEN1 gene in sporadic parathyroid tumors. J Clin Endocrinol Metab 1998;83:2627–2630.
[PubMed]
40.
Teh BT, McArdle J, Parameswaran V, David R, Larsson C, Sheperd JJ: Sporadic primary hyperparathyroidism in the setting of multiple endocrine neoplasia type 1. Arch Surg 1996;131:1230–1232.
[PubMed]
41.
Stock JL, Warth MR, Teh BT, Coderre JA, Overdorf JH, Baumann G, Hintz RL, Hartman ML, Seizinger BR, Larsson C, Aronin N: A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine type 1 locus at chromosome region 11q13. J Clin Endocrinol Metab 1997;82:486–492.
[PubMed]
42.
Kishi M, Tsukada T, Shimizu S, Futami H, Ito Y, Kanbe M, Obara T, Yamaguchi K: 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.
[PubMed]
43.
Donis-Keller H, Dou S, Chi D, Carlson KM, Toshima K, Lairmore TC, Howe JR, Moley JF, Goodfellow P, Wells SA Jr: Mutations in the RET proto-oncogene are associated with MEN2A and FMTC. Hum Mol Genet 1993;2:851–856.
[PubMed]
44.
Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L: Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993;363:458–460.
[PubMed]
45.
Vasen HF, van der Feltz M, Raue F, Kruseman AN, Koppeshaar HP, Pieters G, Seif FJ, Blum WF, Lips CJM: The natural course of multiple endocrine neoplasia type IIb. A study of 118 cases. Arch Intern Med 1992;152:1250–1252.
[PubMed]
46.
Farndon JR, Leight GS, Dilley WG, Baylin SB, Smallridge RC, Harrison TS, Wells SA Jr: Familial medullary thyroid carcinoma without associated endocrinopathies: A distinct clinical entity. Br J Surg 1986;73:278–281.
[PubMed]
47.
van Heurn LW, Schaap C, Sie G, Haagen AA, Gerver WJ, Freling G, van Amstel HK, Heineman E: Predictive DNA testing for multiple endocrine neoplasia 2: A therapeutic challenge of prophylactic thyroidectomy in very young children. J Pediatr Surg 1999;34:568–571.
[PubMed]
48.
Moers AM, Landsvater RM, Schaap C, Jansen-Schillhorn van Veen JM, de Valk IA, Blijham GH, Hoppener JW, Vroom TM, van Amstel HK, Lips CJ: Familial medullary thyroid carcinoma: Not a distinct entity? Genotype-phenotype correlations in a large family. Am J Med 1996:101:635–641.
[PubMed]
49.
Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H: Cloning and expression of the RET proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene 1988;3:571–578.
[PubMed]
50.
Airaksinen MS, Titievsky A, Saarma M: GDNF family neurotrophic factors signalling: Four masters, one servant? Mol Cell Neurosci 1999;13:313–325.
[PubMed]
51.
Taraviras S, Marcos-Gutierrez CV, Durbec P, Jani H, Grigoriou M, Sukumaran M, Wang LC, Hynes M, Raisman G, Pachnis V: Signalling by the RET receptor tyrosine kinase and its rôle in the development of the mammalian enteric nervous system. Development 1999;126:2785–2797.
[PubMed]
52.
Sariola H, Saarma M: GDNF and its receptors in the regulation of the ureteric branching. Int J Dev Biol 1999;43:413–418.
[PubMed]
53.
Ohiwa M, Murakami H, Iwashita T, Asai N, Iwata Y, Imai T, Funahashi H, Takagi H, Takahashi M: Characterization of Ret-Shc-Grb2 complex induced by GDNF, MEN2A, and MEN2B mutations. Biochem Biophys Res Commun 1997;237:747–751.
[PubMed]
54.
Nakamura T, Ishizaka Y, Nagao M, Hara M, Ishikawa T: Expression of the ret proto-oncogene product in human normal and neoplastic tissues of neural crest origin. J Pathol 1994;172:255–260.
[PubMed]
55.
Avantaggiato V, Dathan NA, Grieco M, Fabien N, Lazzaro D, Fusco A, Simeone A, Santoro M: Developmental expression of the RET protooncogene. Cell Growth Differ 1994;5:305–311.
[PubMed]
56.
Kwok JB, Gardner E, Warner JP, Ponder BA, Mulligan LM: Structural analysis of the human ret proto-oncogene using exon trapping. Oncogene 1993;8:2575–2582.
[PubMed]
57.
Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V: Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 1994;367:380–383.
[PubMed]
58.
Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M: Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 1996;382:70–73.
[PubMed]
59.
Enomoto H, Araki T, Jackman A, Heuckeroth RO, Snider WD, Johnson EM Jr, Milbrandt J: GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron 1998;21:317–324.
[PubMed]
60.
Edery P, Lyonnet S, Mulligan LM, Pelet A, Dow E, Abel L, Holder S, Nihoul-Fekete C, Ponder BA, Munnich A: Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994;367:378–380.
[PubMed]
61.
Ponder BA, Smith D: The MEN II syndromes and the role of the ret proto-oncogene. Adv Cancer Res 1996;70:179–222.
[PubMed]
62.
Pasini B, Ceccherini I, Romeo G: RET mutations in human disease. Trends Genet 1996;12:138–144.
[PubMed]
63.
Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjold M, Komminoth P, Hendy GN, Mulligan LM: 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.
[PubMed]
64.
Frank-Raue K, Kratt T, Hoppner W, Buhr H, Ziegler R, Raue F: Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2: Relevance of specific mutations in the RET proto-oncogene. Eur J Endocrinol 1996;135:222–225.
[PubMed]
65.
Schuffenecker I, Virally-Monod M, Brohet R, Goldgar D, Conte-Devolx B, Leclerc L, Chabre O, Boneu A, Caron J, Houdent C, Modigliani E, Rohmer V, Schlumberger M, Eng C, Guillausseau PJ, Lenoir GM: Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2A families with mutations at codon 634 of the RET proto-oncogene. Groupe d’Etude des Tumeurs a Calcitonine. J Clin Endocrinol Metab 1998;83:487–491.
[PubMed]
66.
Santoro M, Carlomagno F, Romano A, Bottaro DP, Dathan NA, Grieco M, Fusco A, Vecchio G, Matoskova B, Kraus MH: Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 1995;267:381–383.
[PubMed]
67.
Michiels FM, Chappuis S, Caillou B, Pasini A, Talbot M, Monier R, Lenoir GM, Feunteun J, Billaud M: Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation. Proc Natl Acad Sci USA 1997;94:3330–3335.
[PubMed]
68.
Hoppner W, Dralle H, Brabant G: Duplication of 9 base pairs in the critical cysteine-rich domain of the RET proto-oncogene causes multiple endocrine neoplasia type 2A. Hum Mutat 1998(suppl 1):128–130.
69.
Pigny P, Bauters C, Wemeau JL, Houcke ML, Crepin M, Caron P, Giraud S, Calender A, Buisine MP, Kerckaert JP, Porchet N: A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinoma. J Clin Endocrinol Metab 1999;84:1700–1704.
[PubMed]
70.
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.
[PubMed]
71.
Berndt I, Reuter M, Saller B, Frank-Raue K, Groth P, Grussendorf M, Raue F, Ritter MM, Hoppner W: 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.
[PubMed]
72.
Eng C, Smith DP, Mulligan LM, Nagai MA, Healey CS, Ponder MA, Gardner E, Scheumann GF, Jackson CE, Tunnacliffe A: 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.
[PubMed]
73.
Rossel M, Pasini A, Chappuis S, Geneste O, Fournier L, Schuffenecker I, Takahashi M, van Grunsven LA, Urdiales JL, Rudkin BB, Lenoir GM, Billaud M: Distinct biological properties of two RET isoforms activated by MEN 2A and MEN 2B mutations. Oncogene 1997;14:265–275.
[PubMed]
74.
Smith DP, Houghton C, Ponder BA: Germline mutation of RET codon 883 in two cases of de novo MEN 2B. Oncogene 1997;15:1213–1217.
[PubMed]
75.
Gimm O, Marsh DJ, Andrew SD, Frilling A, Dahia PL, Mulligan LM, Zajac JD, Robinson BG, Eng C: 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.
[PubMed]
76.
Boccia LM, Green JS, Joyce C, Eng C, Taylor SA, Mulligan LM: Mutation of RET codon 768 is associated with the FMTC phenotype. Clin Genet 1997;51:81–85.
[PubMed]
77.
Hofstra RM, Fattoruso O, Quadro L, Wu Y, Libroia A, Verga U, Colantuoni V, Buys CH: 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.
[PubMed]
78.
Miyauchi A, Egawa S, Futami H, Kuma K, Obara T, Yamaguchi K: 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.
[PubMed]
79.
Fattoruso O, Quadro L, Libroia A, Verga U, Lupoli G, Cascone E, Colantuoni V: A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma. Hum Mutat 1998(suppl 1):167–171.
80.
Dang GT, Cote GJ, Schultz PN, Khorana S, Decker RA, Gagel RF: A codon 891 exon 15 RET proto-oncogene mutation in familial medullary thyroid carcinoma: A detection strategy. Mol Cell Probes 1999;13:77–79.
[PubMed]
81.
Eng C, Mulligan LM, Smith DP, Healey CS, Frilling A, Raue F, Neumann HP, Pfragner R, Behmel A, Lorenzo MJ: Mutation of the RET protooncogene in sporadic medullary thyroid carcinoma. Genes Chromosomes Cancer 1995;12:209–212.
[PubMed]
82.
Wohllk N, Cote GJ, Bugalho MM, Ordonez N, Evans DB, Goepfert H, Khorana S, Schultz P, Richards CS, Gagel RF: Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1996;81:3740–3745.
[PubMed]
83.
Eng C, Mulligan LM, Healey CS, Houghton C, Frilling A, Raue F, Thomas GA, Ponder BA: Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma. Cancer Res 1996;56:2167–2170.
[PubMed]
84.
van der Harst E, de Krijger RR, Bruining HA, Lamberts SW, Bonjer HJ, Dinjes WN, Proye C, Koper JW, Bosman FT, Roth J, Heitz PU, Komminoth P: Prognostic value of RET proto-oncogene point mutations in malignant and benign, sporadic phaeochromocytomas. Int J Cancer 1998;79:537–540.
[PubMed]
85.
Kimura T, Yoshimoto K, Tanaka C, Ohkura T, Iwahana H, Miyauchi A, Sano T, Itakura M: Obvious mRNA and protein expression but absence of mutations of the RET proto-oncogene in parathyroid tumors. Eur J Endocrinol 1996;134:314–319.
[PubMed]
86.
Pausova Z, Soliman E, Amizuka N, Janicic N, Konrad EM, Arnold A, Goltzman D, Hendy GN: Role of the RET proto-oncogene in sporadic hyperparathyroidism and in hyperparathyroidism of multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 1996;81:2711–2718.
[PubMed]
87.
Komminoth P, Roth J, Muletta-Feurer S, Saremaslani P, Seelentag WK, Heitz PU: RET proto-oncogene point mutations in sporadic neuroendocrine tumors.J Clin Endocrinol Metab 1996;81:2041–2046.
[PubMed]
88.
Smith DP, Houghton C, Ponder BA: Germline mutation of RET codon 883 in two cases of de novo MEN 2B. Oncogene 1997;15:1213–1217.
[PubMed]
89.
Kitamura Y, Scavarda N, Wells SA Jr, Jackson CE, Goodfellow PJ: Two maternally derived missense mutations in the tyrosine kinase domain of the RET protooncogene in a patient with de novo MEN 2B. Hum Mol Genet 1995;4:1987–1988.
[PubMed]
90.
Modigliani E, Vasen HM, Raue K, Dralle H, Frilling A, Gheri RG, Brandi ML, Limbert E, Niederle B, Forgas L and the GETC: Pheochromocytoma in multiple endocrine neoplasia type 2: European study. The Euromen Study Group. J Intern Med 1995;238:363–367.
[PubMed]
91.
Richard S, Giraud S, Beroud C, Caron J, Penfornis F, Baudin E, Niccoli-Sire P, Murat A, Schlumberger M, Plouin PF, Conte-Devolx B and the Francophone Study Group of von Hippel-Lindau Disease (GEVHL): Von Hippel-Lindau disease: Recent genetic progress and patient management. Ann Endocrinol 1998;59:452–458.
92.
Neumann HPH, Dinkel E, Brambs H, Wimmer B, Friedburg H, Volk B, Sigmund G, Riegler P, Haag K, Schollmeyer P, Wiestler OD: Pancreatic lesions in the von Hippel-Lindau syndrome. Gastroenterology 1991;101:465–471.
[PubMed]
93.
Lubensky IA, Pack S, Ault D, Vortmeyer AO, Libutti SK, Choyke PL, Walther MM, Linehan WM, Zhuang Z: Multiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease patients: Histopathological and molecular genetic analysis. Am J Pathol 1998;153:223–231.
[PubMed]
94.
Neumann HPH, Dinkel E, Brambs H, Wimmer B, Friedburg H, Volk B, Sigmund G, Riegler P, Haag K, Schollmeyer P, Wiestler OD: Pancreatic lesions in the von Hippel-Lindau syndrome. Gastroenterology 1991;101:465–471.
[PubMed]
95.
Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, Schmidt L, Zhou F, Li H, Wei MH, Chen F, Glenn G, Choyke P, Walther MC, Weng Y, Duan DSR, Dean M, Glavac D, Richards FM, Crossey PA, Ferguson-Smith MA, Le Paslier D, Chumakov I, Cohen D, Chinault C, Maher ER, Linehan WM, Zbar B, Lerman MI: Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993;260:1317–1320.
[PubMed]
96.
Aso T, Lane WS, Conaway JW, Conaway RC: Elongin (SIII): A multisubunit regulator of elongation by RNA polymerase II. Science 1995;269:1439–1443.
[PubMed]
97.
Kibel A, Iliopoulos O, DeCaprio JA, Kaelin WG Jr: Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science 1995;269:1444–1446.
[PubMed]
98.
Lubensky IA, Pack S, Ault D, Vortmeyer AO, Libutti SK, Choyke PL, Walther MM, Linehan WM, Zhuang Z: Multiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease patients: Histopathological and molecular genetic analysis. Am J Pathol 1998;153:223–231.
[PubMed]
99.
Vortmeyer AO, Lubensky IA, Fogt F, Linehan WM, Khettry U, Zhuang Z: Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. Am J Pathol 1997;51:951–956.
100.
Swinburn BA, Yeong ML, Lane MR, Nicholson GI, Holdaway IM: Neurofibromatosis associated with somatostinoma: A report of two patients. Clin Endocrinol (Oxf) 1988;28:353–359.
[PubMed]
101.
Van Basten JP, Van Hoek B, De Bruine A, Arends JW, Stockbrugger RW: Ampullary carcinoid and neurofibromatosis: Case report and review of the litterature. Neth J Med 1994;44:202–206.
[PubMed]
102.
Reichardt M, Rexroth W, Hasslacher C: Von Recklighausen type I neurofibromatosis and neuroendocrine tumor (somatostatinoma) in a 50-year old woman. Med Klin 1998;93:550–553.
[PubMed]
103.
Kim H, Kerr A, Morehouse H: The association between tuberous sclerosis and insulinoma. Am J Neuroradiol 1995;16:1543–1544.
[PubMed]
104.
Verhoef S, van Diemen-Steenvoorde R, Akkersdijk WL, Bax NM, Ariyurek Y, Hermans CJ, van Nieuwenhuizen O, Nikkels PG, Lindhout D, Halley DJ, Lips K, van den Ouweland AM: Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood Eur J Pediatr 1999;158:284–287.
105.
Ballester R, Marchuk D, Boguski M, Saulino A, Letcher R, Wigler M, Collins F: The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 1990;63:851–859.
[PubMed]
106.
Xiao GH, Shoarinejad F, Jin F, Golemis EA, Yeung RS: The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. J Biol Chem 1997;272:6097–6100.
[PubMed]
107.
van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Kwiatkowski DJ: Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997;277:805–808.
[PubMed]
108.
van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P: Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 1998;7:1053–1057.
[PubMed]
109.
Plank TL, Yeung RS, Henske EP: Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Res 1998;58:4766–4770.
[PubMed]
110.
Friedman E, Sakaguchi K, Bale AE, Falchetti A, Streeten E, Zimering MB, Weinstein LS, McBride WO, Nakamura Y, Brandi ML: Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1 (MEN1). N Engl J Med 1989;321:213–218.
[PubMed]
111.
Goebel SU, Vortmeyer AO, Zhuang ZP, Serrano J, Jensen RT, Lubensky IA: Identical clonality of sporadic gastrinomas at multiple sites. Cancer Res 2000;60:60–63.
[PubMed]
112.
Farnebo F, Farnebo LO, Nordenstrom J, Larsson C: Allelic loss on chromosome 11 is uncommon in parathyroid glands of patients with hypercalcaelmic secondary hyperparathyroidism. Eur J Surg 1997;163:331–337.
[PubMed]
113.
Tomassetti P, Cometa G, Del Vecchio E, Baserga M, Faccioli P, Bosoni D, Paolucci G, Barbara L: Chromosomal instability in multiple endocrine neoplasia type 1: Cytogenetic evaluation with DEB test. Cancer Genet Cytogenet 1995;79:123–126.
[PubMed]
114.
Sakurai A, Katai M, Itakura Y, Ikeo Y, Hashizume K: Premature centromere division in patients with multiple endocrine neoplasia type 1. Cancer Genet Cytogenet 1999;109:138–140.
[PubMed]
115.
Brandi ML, Marx SJ, Aurbach GD, Fitzpatrick LA: Familial multiple endocrine neoplasia type 1: A new look at physiopathology. Endocr Rev 1992;13:391–405.
116.
Zimering MB, Katsumata N, Friesen HG, Eng J, Riley DJ, Thakker-Varia S, Marx SJ, Ezzat S: Fibroblast growth factor-like autoantibodies in plasma from patients with multiple endocrine neoplasia type 1 and prolactinoma. Ann NY Acad Sci 1997;815:520–523.
[PubMed]
117.
Smith-Hicks CL, Sizer KC, Powers JF, Tischler AS, Costantini F: C-cell hyperplasia, pheochromocytoma and sympathoadrenal malformation in a mouse model of multiple endocrine neoplasia type 2B. EMBO J 2000;19:612–622.
[PubMed]
118.
Asai N, Murakami H, Iwashita T, Takahashi M: A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with shc adaptor proteins. J Biol Chem 1996;27:17644–17649.
119.
Liu X, Vega QC, Decker RA, Pandey A, Worby CA, Dixon JE: Oncogenic RET receptors display different autophosphorylation sites and substrate binding specificities. J Biol Chem 1996;271:5309–5312.
[PubMed]
120.
Lorenzo MJ, Gish GD, Houghton C, Stonehouse TJ, Pawson T, Ponder BA, Smith D: RET alternate splicing influences the interaction of activated RET with the SH2 and PTB domains of Shc, and the SH2 domain of Grb2. Oncogene 1997;14:763–771.
[PubMed]
121.
Alberti L, Borrello MG, Ghizzoni S, Torriti F, Rizzetti MG, Pierotti M: Grb2 binding to the different isoforms of Ret tyrosine kinase. Oncogene 1998;17:1079–1087.
[PubMed]
122.
Segouffin-Cariou C, Billaud M: Transforming ability of MEN2A-RET requires activation of the phosphatidylinositol 3-kinase/AKT signaling pathway. J Biol Chem 2000;275:3568–3576.
[PubMed]
123.
Murakami H, Iwashita T, Asai N, Shimono Y, Iwata Y, Kawai K, Takahashi M: Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of its downstream signalling molecules mediated by ret with the MEN 2B mutation. Biochem Biophys Res Commun 1999;262:68–75.
[PubMed]
124.
Chappuis-Flament S, Pasini A, De Vita G, Segouffin-Cariou C, Fusco A, Attie T, Lenoir GM, Santoro M, Billaud M: Dual effect on the RET receptor of MEN 2 mutations affecting specific extracytoplasmic cysteines. Oncogene 1998;17:2851–2861.
[PubMed]
125.
Carlomagno F, Salvatore G, Cirafici AM, De Vita G, Melillo RM, de Franciscis V, Billaud M, Fusco A, Santoro M: The different RET-activating capability of mutations of cysteine 620 and cysteine 634 correlates with the multiple endocrine neoplasia type 2 disease phenotype. Cancer Res 1997;57:391–395.
[PubMed]
126.
Borrego S, Eng C, Sanchez B, Saez ME, Navarro E, Antinolo G: Molecular analysis of the RET and GDNF genes in a family with multiple endocrine neoplasia type 2A and Hirschsprung disease. J Clin Endocrinol Metab 1998;83:3361–3364.
[PubMed]
127.
Lee S, Neumann M, Stearman R, Stauber R, Pause A, Pavlakis GN, Klausner RD: Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein. Mol Cell Biol 1999;19:1486–1497.
[PubMed]
128.
Knebelmann B, Ananth S, Cohen HT, Sukhatme V: Transforming growth factor alpha is a target for the von Hippel-Lindau tumor suppressor. Cancer Res 1998;58:226–231.
[PubMed]
129.
Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme V: The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. Mol Cell Biol 1997;17:5629–5639.
[PubMed]
130.
Ananth S, Knebelmann B, Gruning W, Dhanabal M, Walz G, Stillman IE, Sukhatme V: Transforming growth factor beta1 is a target for the von Hippel-Lindau tumor suppressor and a critical growth factor for clear cell renal carcinoma. Cancer Res 1999;59:2210–2216.
[PubMed]
131.
Lonergan KM, Iliopoulos O, Ohh M, Kamura T, Conaway RC, Conaway JW, Kaelin WG Jr: Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. Mol Cell Biol 1998;18:732–741.
[PubMed]
132.
Kamura T, Conrad MN, Yan Q, Conaway RC, Conaway JW: The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2. Genes Dev 1999;13:2928–2933.
[PubMed]
133.
Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG Jr, Elledge SJ, Conaway RC, Harper JW, Conaway JW: Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 1999;284:657–661.
[PubMed]
134.
Przygodzki RM, Finkelstein SD, Langer JC, Swalsky PA, Fishback N, Bakker A, Guinee DG, Koss M, Travis WD: Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. Am J Pathol 1996;148:1131–1141.
135.
Bartz C, Ziske C, Wiedenmann B, Moelling K: p53 tumour suppressor gene expression in pancreatic neuroendocrine tumour cells. Gut 1996;38:403–409.
[PubMed]
136.
Wiethege T, Voss B, Muller Karim MA: P53 accumulation and proliferating-cell nuclear antigen expression in human lung cancer. J Cancer Res Clin Oncol 1995;121:371–377.
[PubMed]
137.
Wagner SN, Muller R, Boehm J, Putz B, Wunsch PH, Hofler H: Neuroendocrine neoplasms of the lung are not associated with point mutations at codon 12 of the Ki-ras gene. Virchows Arch B Cell Pathol Incl Mol Pathol 1993;63:325–329.
[PubMed]
138.
Evers BM, Rady PL, Tyring SK, Sanchez RL, Rajamaran S, Towsend CM Jr, Thomson JC: Amplification of the HER/neu protooncogene in human neuroendocrine tumors. Surgery 1992;112:211–217.
[PubMed]
139.
Arany I, Rady P, Evers BM, Tyring SK, Towsend CM Jr: Analysis of multiple molecular changes in human endocrine tumors. Surg Oncol 1994;3:153–159.
[PubMed]
140.
Sagara M, Sugiyama F, Horiguchi H, Kamma H, Ogata T, Yagami K, Murakami K, Fukamizu A: Activation of the nuclear oncogenes N-myc and C-jun in carcinoid tumors of transgenic mice carrying the human adenovirus type 12 E1 antigen. DNA Cell Biol 1995;14:95–101.
[PubMed]
141.
Terris B, Meddeb M, Marchio A, Danglot G, Flejou JF, Belghiti J, Ruszniewski P, Bernheim A: Comparative genomic hybridization analysis of sporadic neuroendocrine tumors of the digestive system. Genes Chromosomes Cancer 1998;22:50–56.
[PubMed]
142.
Wang DG, Johnston CF, Buchanan KD: Oncogene expression in gastroenteropancreatic neuroendocrine tumors: Implications for pathogenesis. Cancer 1997;80:668–675.
[PubMed]
143.
Scwindinger WF, Francomano CA, Levine MA: Identification of a mutation in the gene encoding the α subunit of the stimulatory G protein of adenylyl-cyclase in McCune-Albright syndrome. Proc Natl Acad Sci USA 1992;89:5152–5156.
[PubMed]
144.
Boothroyd CV, Grimmond SM, Cameron DP, Hayward NK: G protein mutations in tumours of the pituitary, parathyroid and endocrine pancreas. Biochem Biophys Res Commun 1995;211:1063–1070.
[PubMed]
145.
Arnold A, Motokura T, Bloom T, Rosenberg C, Bale A, Kronenberg H, Ruderman J, Brown M, Kim HG: PRAD1 (cyclin D1): A parathyroid neoplasia gene on 11q13. Henry Ford Hosp Med J 1992;40:177–180.
[PubMed]
146.
Tominaga Y, Tsuzuki T, Uchida K, Haba T, Otsuka S, Ichimori T, Yamada K, Numano M, Tanaka Y, Takagi H: Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma. Kidney Int 1999;55:1375–1383.
[PubMed]
147.
Ebrahimi SA, Wang EH, Wu A, Schreck RR, Passaro E Jr, Sawicki MP: Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors. Cancer Res 1999;59:311–315.
[PubMed]
148.
Chakrabarti R, Srivatsan ES, Wood TF, Eubanks PJ, Ebrahimi SA, Gatti RA, Passaro E Jr, Sawicki MP: Deletion mapping of endocrine tumors localizes a second tumor suppressor gene on chromosome band 11q13. Genes Chromosomes Cancer 1998;22:130–137.
[PubMed]
149.
Chung DC, Smith AP, Louis DN, Graeme-Cook F, Warshaw AL, Arnold J: A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications. J Clin Invest 1997;100:404–410.
[PubMed]
150.
Hessman O, Lindberg D, Einarsson A, Lillhager P, Carling T, Grimelius L, Eriksson B, Akerstrom G, Westin G, Skogseid B. Genetic alterations on 3p, 11q13, and 18q in non familial and MEN1-associated pancreatic endocrine tumors. Genes Chromosomes Cancer 1999;26:258–264.
[PubMed]
151.
Chung DC, Brown SB, Graeme-Cooke F, Tillotson LG, Warshaw AL, Jensen RT, Arnold A: Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors. Cancer Res 1998;58:3706–3711.
[PubMed]
152.
Nikiforova MN, Nikiforov YE, Gnepp DR, Gnepp DR, Grosembacher LA, Wajchenberg BL, Fagin JA, Cohen RM: Frequent loss of heterozygosity at chromosome 3p14.2–3p21 in human pancreatic islet cell tumors. Clin Endocrinol 1999;51:27–34.
153.
Sozzi G, Veronese ML, Negrini M, et al: The FIHT gene 3p14.2 is abnormal in lung cancer. Cell 1996;85:587–597.
154.
Gaudino G, Avantaggiato V, Follenzi A, Acampora D, Simeone A, Comoglio RM: The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues. Oncogene 1995;11:2627–2637.
[PubMed]
155.
Santoro MM, Penengo L, Minetto M, Orecchia S, Cilli M, Gaudino G: Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the Ron receptor. Oncogene 1998;17:741–749.
[PubMed]
156.
Okh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov AO, Louis DN, Gavin BJ, Kley N, Kaelin WG Jr, Iliopoulos O: The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Mol Cell 1998;7:959–968.
157.
Onuki N, Wistuba H, Travis WD, Virmani AK, Yashima K, Brambilla E, Hasleton P, Gazda AF: Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer Res 1999;85:600–607.
158.
Shi YP, Naik P, Dietrich WF, Gray JW, Hanahan D, Pinkel D: DNA copy number changes associated with characteristic LOH in islet cell carcinomas of transgenic mice. Genes Chromosomes Cancer 1997;19:104–111.
[PubMed]
159.
Muscarella P, Scott Melwin W, Fisher WE, Foor J, Ellison C, Herman JG, Scirmer WJ, Hitchcock CL, DeYoung BR, Weghorst CM: Genetic alterations in gastrinomas and nonfunctioning pancreatic endocrine tumors: An analysis of p16/MTS1 tumour suppressor gene inactivation. Cancer Res 1998;58:237–240.
[PubMed]
160.
Naumann M, Savitskaia N, Eilert C, Schramm A, Kalthoff H, Schmiegel W: Frequent codeletion of p16/MTS1 and p15/MTS2 and genetic alterations in p16/MTS1 in pancreatic tumors. Gastroenterology 1996;110:1215–1124.
[PubMed]
161.
Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin S: Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 1995;55:4525–4530.
[PubMed]
162.
Nilsson O, Wangberg B, Kolby L, Schultz GS, Ahlman H: Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumors. Int J Cancer 1995;60:645–651.
[PubMed]
163.
Bold RJ, Ishikuza J, Rajamaran S, Perez-Polo JR, Towsend CM Jr, Thompson JC: Nerve growth factor as a mitogen for a pancreatic carcinoid cell line. J Neurochem 1995;64:2622–2628.
[PubMed]
164.
Grimmond S, Lagercrantz J, Drinkwater C, Silins G, Townson S, Pollock P, Gotley D, Carson E, Rakar S, Nordenskjöld M, Ward L, Hayward NK, Weber G: Cloning and characterization of a novel human gene related to vascular endothelial growth factor. Genome Res 1996;6:124–131.
[PubMed]
165.
Liu B, Earl HM, Baban D, Shobaibi M, Fabra A, Kerr DJ, Seymour LW: Melanoma cell lines express VEGF receptor KDR and respond to exogenously added VEGF. Biochim Biophys Res Commun 1995;217:721–727.
166.
Terris B, Fléiou F, Dubois S, Rusniewski P, Belghiti J, Potet N, Bernades P, Mignon M, Hénin D: Increased expression of CD44v6 in endocrine pancreatic tumors but not in midgut carcinoid tumors. AGA report (abstract). Gastroenterology 1996;110:A437.
167.
Moller CJ, Christgau S, Williamson MR, Madsen OD, Niu ZP, Bock E, Baekkeskov S: Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. Mol Endocrinol 1992;8:1332–1342.
168.
Dahl U, Sjodin A, Semb H: Cadherins regulate aggregation of pancreatic beta-cells in vivo. Development 1996;122:2895–2902.
[PubMed]
You do not currently have access to this content.