Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology

Cellular and Molecular Gastroenterology and Hepatology

Volumn 1, Issue 2, 2015, Pages 131-153

  Kidd, Mark ^a   Modlin, Irvin M ^a   Bodei, Lisa ^a   Drozdov, Ignat ^a  

^a The Gnostic Consortium Wren Laboratories   (United States)

Author keywords

Blood; Carcinoid; Gastroenteropancreatic Neuroendocrine Neoplasms; Ki 67; Proliferation; Somatostatin; Transcriptome

Indexed keywords

ATAXIA TELANGIECTASIA MUTATED KINASE; MEMBRANE RECEPTOR; PHOSPHOTRANSFERASE; PROTEIN KINASE B; PROTEIN P27; SOMATOSTATIN RECEPTOR; UNCLASSIFIED DRUG;

CARCINOID; CELL PROLIFERATION; CELL STRUCTURE; DNA SEQUENCE; EXTRACELLULAR MATRIX; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR; GENE MUTATION; HISTOPATHOLOGY; HUMAN; INTRACELLULAR SIGNALING; METASTASIS; METASTASIS ASSOCIATED 1 GENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SECRETORY CELL; SIGNAL TRANSDUCTION; SMALL INTESTINE; TRANSCRIPTOMICS; TUMOR SUPPRESSOR GENE;

EID: 84928949704     PISSN: None     EISSN: 2352345X     Source Type: Journal    
DOI: 10.1016/j.jcmgh.2014.12.008     Document Type: Review

References (213)

1. Modlin I.M., Oberg K., Chung D.C., et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008, 9:61-72.
2. Strosberg J. Evolving treatment strategies for management of carcinoid tumors. Curr Treat Options Oncol 2013, 14:374-388.
3. Baudin E., Planchard D., Scoazec J.Y., et al. Intervention in gastro-enteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol 2012, 26:855-865.
4. Modlin I.M., Kidd M., Latich I., et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005, 128:1717-1751.
5. Yao J.C., Hassan M., Phan A., et al. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. JClin Oncol 2008, 26:3063-3072.
6. Ellis L., Shale M.J., Coleman M.P. Carcinoid tumors of the gastrointestinal tract: trends in incidence in England since 1971. Am J Gastroenterol 2010, 105:2563-2569.
7. Maggard M.A., O'Connell J.B., Ko C.Y. Updated population-based review of carcinoid tumors. Ann Surg 2004, 240:117-122.
8. Lawrence B., Gustafsson B.I., Chan A., et al. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am 2011, 40:1-18. vii.
9. Modlin I.M., Moss S.F., Chung D.C., et al. Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. JNatl Cancer Inst 2008, 100:1282-1289.
10. Powell A.C., Libutti S.K. Multiple endocrine neoplasia type 1: clinical manifestations and management. Cancer Treat Res 2010, 153:287-302.
11. de Mestier L., Dromain C., d'Assignies G., et al. Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art. Endocr Relat Cancer 2014, 21:R105-R120.
12. Bergsland E.K. The evolving landscape of neuroendocrine tumors. Semin Oncol 2013, 40:4-22.
13. Wang H., Chen Y., Fernandez-Del Castillo C., et al. Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway. Mod Pathol 2012, 24:143.
14. Sundin A., Rockall A. Therapeutic monitoring of gastroenteropancreatic neuroendocrine tumors: the challenges ahead. Neuroendocrinology 2012, 96:261-271.
15. Kidd M., Schimmack S., Lawrence B., et al. EGFR/TGFα and TGFβ/CTGF signaling in neuroendocrine neoplasia: theoretical therapeutic targets. Neuroendocrinology 2012, 15:15.
16. Chan J.A., Kulke M.H. New treatment options for patients with advanced neuroendocrine tumors. Curr Treat Options Oncol 2011, 12:136-148.
17. Oberg K. Pancreatic endocrine tumors. Semin Oncol 2010, 37:594-618.
18. Garcia-Carbonero R., Capdevila J., Crespo-Herrero G., et al. Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol 2010, 21:1794-1803.
19. Strosberg J., Gardner N., Kvols L. Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors of the mid-gut. Neuroendocrinology 2009, 89:471-476.
20. Frilling A., Akerstrom G., Falconi M., et al. Neuroendocrine tumor disease: an evolving landscape. Endocr Relat Cancer 2012, 19:R163-R185.
21. Frilling A., Modlin I., Kidd M., et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol 2014, 15:e8-e21.
22. Sippel R.S., Chen H. Carcinoid tumors. Surg Oncol Clin N Am 2006, 15:463-478.
23. Ramage J.K., Ahmed A., Ardill J., et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012, 61:6-32.
24. Eisenhauer E.A., Therasse P., Bogaerts J., et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009, 45:228-247.
25. Neperud J., Mahvash A., Garg N., et al. Can imaging patterns of neuroendocrine hepatic metastases predict response yttruim-90 radioembolotherapy?. World J Radiol 2013, 5:241-247.
26. Denecke T., Baur A.D., Ihm C., et al. Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors. Eur J Radiol 2013, 82:e550-e555.
27. Oberg K., Kvols L., Caplin M., et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004, 15:966-973.
28. Caplin M.E., Pavel M., Cwikla J.B., et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. NEngl J Med 2014, 371:224-233.
29. Rinke A., Muller H.H., Schade-Brittinger C., et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. JClin Oncol 2009, 27:4656-4663.
30. Yao J.C., Phan A., Hoff P.M., et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. JClin Oncol 2008, 26:1316-1323.
31. Yao J.C., Shah M.H., Ito T., et al. Everolimus for advanced pancreatic neuroendocrine tumors. NEngl J Med 2011, 364:514-523.
32. Raymond E., Dahan L., Raoul J.L., et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. NEngl J Med 2011, 364:501-513.
33. Lawrence B., Gustafsson B.I., Kidd M., et al. New pharmacologic therapies for gastroenteropancreatic neuroendocrine tumors. Gastroenterol Clin North Am 2010, 39:615-628.
34. Qi W.X., Huang Y.J., Yao Y., et al. Incidence and risk of treatment-related mortality with mTOR inhibitors everolimus and temsirolimus in cancer patients: a meta-analysis. PLoS ONE 2013, 8:e65166.
35. Yao J.C., Lagunes D.R., Kulke M.H. Targeted therapies in neuroendocrine tumors (NET): clinical trial challenges and lessons learned. Oncologist 2013, 18:525-532.
36. Champaneria M.C., Modlin I.M., Kidd M., et al. Friedrich Feyrter: a precise intellect in a diffuse system. Neuroendocrinology 2006, 83:394-404.
37. Peto R., Roe F.J., Lee P.N., et al. Cancer and ageing in mice and men. Br J Cancer 1975, 32:411-426.
38. Frank S.A. Dynamics of cancer: incidence, inheritance, and evolution 2007, Princeton University Press, Princeton, NJ.
39. Berge T., Linell F. Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand A 1976, 84:322-330.
40. Gustafsson B.I., Kidd M., Modlin I.M. Neuroendocrine tumors of the diffuse neuroendocrine system. Curr Opin Oncol 2008, 20:1-12.
41. McGinnis N. The unexpected applicability of paraconsistent logic: a Chomskyan route to dialetheism. Found Sci 2013, 18:625-640.
42. Kloppel G., Perren A., Heitz P.U. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann NY Acad Sci 2004, 1014:13-27.
43. Kidd M., Hauso O., Drozdov I., et al. Delineation of the chemomechanosensory regulation of gastrin secretion using pure rodent G cells. Gastroenterology 2009, 137:231-241. e1-e10.
44. Gustafsson B.I., Bakke I., Tommeras K., et al. Anew method for visualization of gut mucosal cells, describing the enterochromaffin cell in the rat gastrointestinal tract. Scand J Gastroenterol 2006, 41:390-395.
45. Bohorquez D.V., Liddle R.A. Axon-like basal processes inenteroendocrine cells: characteristics and potential targets. Clin Transl Sci 2011, 4:387-391.
46. Kidd M., Gustafsson B.I., Drozdov I., et al. IL1β- and LPS-induced serotonin secretion is increased in EC cells derived from Crohn's disease. Neurogastroenterol Motil 2009, 21:439-450.
47. Hauso O., Gustafsson B.I., Waldum H.L. Long slender cytoplasmic extensions: a common feature of neuroendocrine cells?. JNeuroendocrinol 2007, 19:739-742.
48. Schimmack S., Lawrence B., Svejda B., et al. The clinical implications and biologic relevance of neurofilament expression in gastroenteropancreatic neuroendocrine neoplasms. Cancer 2012, 118:2763-2775.
49. Ardill J.E., Erikkson B. The importance of the measurement of circulating markers in patients with neuroendocrine tumours of the pancreas and gut. Endocr Relat Cancer 2003, 10:459-462.
50. Kidd M., Modlin I.M., Gustafsson B.I., et al. Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol 2008, 295:G260-G272.
51. Wiedenmann B., John M., Ahnert-Hilger G., et al. Molecular and cell biological aspects of neuroendocrine tumors of the gastroenteropancreatic system. JMol Med 1998, 76:637-647.
52. Bloom S.R. Gut hormones. Proc Nutr Soc 1978, 37:259-271.
53. Bloom S.R. Gut hormones 1978, Churchill Livingstone, Edinburgh.
54. Modlin I.M., Gustafsson B.I., Moss S.F., et al. Chromogranin A-biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol 2010, 17:2427-2443.
55. 2+-dependent reversible docking of granules to the plasma membrane. Traffic 2002, 3:496-511.
56. Portela-Gomes G.M., Stridsberg M. Selective processing of chromogranin A in the different islet cells in human pancreas. JHistochem Cytochem 2001, 49:483-490.
57. Marotta V., Nuzzo V., Ferrara T., et al. Limitations of chromogranin A in clinical practice. Biomarkers 2012, 17:186-191.
58. Kanakis G., Kaltsas G. Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Best Pract Res Clin Gastroenterol 2012, 26:791-802.
59. Lawrence B., Gustafsson B.I., Kidd M., et al. The clinical relevance of chromogranin A as a biomarker for gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am 2011, 40:111-134. viii.
60. Giovinazzo F., Schimmack S., Svejda B., et al. Chromogranin A and its fragments as regulators of small intestinal neuroendocrine neoplasm proliferation. PLoS ONE 2013, 8:e81111.
61. Wank S.A. Gprotein-coupled receptors in gastrointestinal physiology. I. CCK receptors: an exemplary family. Am J Physiol 1998, 274:G607-G613.
62. Alvarez J. Calcium dynamics in the secretory granules of neuroendocrine cells. Cell Calcium 2012, 51:331-337.
63. Drews G., Krippeit-Drews P., Dufer M. Electrophysiology of islet cells. Adv Exp Med Biol 2010, 654:115-163.
64. Cases A.I., Ohtsuka T., Fujino M., et al. Expression of glucagon-like peptide 1 receptor and its effects on biologic behavior in pancreatic neuroendocrine tumors. Pancreas 2014, 43:1-6.
65. Hook V., Toneff T., Baylon S., et al. Differential activation of enkephalin, galanin, somatostatin, NPY, and VIP neuropeptide production by stimulators of protein kinases A and C in neuroendocrine chromaffin cells. Neuropeptides 2008, 42:503-511.
66. Garcia-Osta A., Del Rio J., Frechilla D. Increased CRE-binding activity and tryptophan hydroxylase mRNA expression induced by 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in the rat frontal cortex but not in the hippocampus. Brain Res Mol Brain Res 2004, 126:181-187.
67. Chin A., Svejda B., Gustafsson B.I., et al. The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion. Am J Physiol Gastrointest Liver Physiol 2012, 302:G397-G405.
68. Papadopulos A., Martin S., Tomatis V.M., et al. Secretagogue stimulation of neurosecretory cells elicits filopodial extensions uncovering new functional release sites. JNeurosci 2013, 33:19143-19153.
69. Reubi J.C., Schonbrunn A. Illuminating somatostatin analog action at neuroendocrine tumor receptors. Trends Pharmacol Sci 2013, 34:676-688.
70. Tentler J.J., Hadcock J.R., Gutierrez-Hartmann A. Somatostatin acts by inhibiting the cyclic 3',5'-adenosine monophosphate (cAMP)/protein kinase A pathway, cAMP response element-binding protein (CREB) phosphorylation, and CREB transcription potency. Mol Endocrinol 1997, 11:859-866.
71. 1 cells by depolarization. JBiol Chem 2001, 276:31667-31673.
72. Rozengurt E., Walsh J.H. Gastrin, CCK, signaling, and cancer. Ann Rev Physiol 2001, 63:49-76.
73. Chalmers C.J., Gilley R., March H.N., et al. The duration of ERK1/2 activity determines the activation of c-Fos and Fra-1 and the composition and quantitative transcriptional output of AP-1. Cell Signal 2007, 19:695-704.
74. Treinies I., Paterson H.F., Hooper S., et al. Activated MEK stimulates expression of AP-1 components independently of phosphatidylinositol 3-kinase (PI3-kinase) but requires a PI3-kinase signal To stimulate DNA synthesis. Mol Cell Biol 1999, 19:321-329.
75. Kinoshita Y., Nakata H., Kishi K., et al. Comparison of the signal transduction pathways activated by gastrin in enterochromaffin-like and parietal cells. Gastroenterology 1998, 115:93-100.
76. Abraham N.S. Proton pump inhibitors: potential adverse effects. Curr Opin Gastroenterol 2012, 28:615-620.
77. Lawrence B., Kidd M., Svejda B., et al. Aclinical perspective on gastric neuroendocrine neoplasia. Curr Gastroenterol Rep 2011, 13:101-109.
78. Berna M.J., Annibale B., Marignani M., et al. Aprospective study of gastric carcinoids and enterochromaffin-like cell changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors. JClin Endocrinol Metab 2008, 93:1582-1591.
79. Furukawa M., Raffeld M., Mateo C., et al. Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases. Clin Cancer Res 2005, 11:3233-3242.
80. Kidd M., Modlin I.M., Pfragner R., et al. Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor-β1-mediated regulatory abnormalities including up-regulation of C-Myc and MTA1. Cancer 2007, 109:2420-2431.
81. Papouchado B., Erickson L.A., Rohlinger A.L., et al. Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas. Mod Pathol 2005, 18:1329-1335.
82. Wulbrand U., Wied M., Zofel P., et al. Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours. Eur J Clin Invest 1998, 28:1038-1049.
83. Nilsson O., Wangberg B., Kolby L., et al. Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumours. Int J Cancer 1995, 60:645-651.
84. Gilbert J.A., Adhikari L.J., Lloyd R.V., et al. Molecular markers for novel therapies in neuroendocrine (carcinoid) tumors. Endocr Relat Cancer 2010, 17:623-636.
85. Krishnamurthy S., Dayal Y. Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids. Am J Surg Pathol 1997, 21:327-333.
86. Susini C., Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 2006, 17:1733-1742.
87. Theodoropoulou M., Stalla G.K. Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol 2013, 34:228-252.
88. Wolin E.M. The expanding role of somatostatin analogs in the management of neuroendocrine tumors. Gastrointest Cancer Res 2012, 5:161-168.
89. Li H.J., Kapoor A., Giel-Moloney M., et al. Notch signaling differentially regulates the cell fate of early endocrine precursor cells and their maturing descendants in the mouse pancreas and intestine. Dev Biol 2012, 371:156-169.
90. Nakakura E.K., Sriuranpong V.R., Kunnimalaiyaan M., et al. Regulation of neuroendocrine differentiation in gastrointestinal carcinoid tumor cells by notch signaling. JClin Endocrinol Metab 2005, 90:4350-4356.
91. Fendrich V., Waldmann J., Esni F., et al. Snail and Sonic Hedgehog activation in neuroendocrine tumors of the ileum. Endocr Relat Cancer 2007, 14:865-874.
92. Shida T., Furuya M., Nikaido T., et al. Sonic Hedgehog-Gli1 signaling pathway might become an effective therapeutic target in gastrointestinal neuroendocrine carcinomas. Cancer Biol Ther 2006, 5:1530-1538.
93. Di Florio A., Adesso L., Pedrotti S., et al. Src kinase activity coordinates cell adhesion and spreading with activation of mammalian target of rapamycin in pancreatic endocrine tumour cells. Endocr Relat Cancer 2011, 18:541-554.
94. Porta C., Paglino C., Mosca A. Targeting PI3K/Akt/mTOR Signaling in Cancer. Front Oncol 2014, 4:64.
95. Silva J.M., Bulman C., McMahon M. BRAFV600E cooperates with PI3K signaling, independent of Akt, to regulate melanoma cell proliferation. Mol Cancer Res 2014, 12:447-463.
96. Svejda B., Kidd M., Kazberouk A., et al. Limitations in small intestinal neuroendocrine tumor therapy by mTOR kinase inhibition reflect growth factor-mediated PI3K feedback loop activation via ERK1/2 and Akt. Cancer 2011, 117:4141-4154.
97. Rozengurt E., Soares H.P., Sinnet-Smith J. Suppression of feedback loops mediated by PI3K/mTOR induces multiple overactivation of compensatory pathways: an unintended consequence leading to drug resistance. Mol Cancer Ther 2014, 13:2477-2488.
98. Tannapfel A., Vomschloss S., Karhoff D., et al. BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors. Am J Clin Pathol 2005, 123:256-260.
99. Perren A., Schmid S., Locher T., et al. BRAF and endocrine tumors: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors. Endocr Relat Cancer 2004, 11:855-860.
100. Karhoff D., Sauer S., Schrader J., et al. Rap1/B-Raf signaling is activated in neuroendocrine tumors of the digestive tract and Raf kinase inhibition constitutes a putative therapeutic target. Neuroendocrinology 2007, 85:45-53.
101. Wang L., Ignat A., Axiotis C.A. Differential expression of the PTEN tumor suppressor protein in fetal and adult neuroendocrine tissues and tumors: progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms. Appl Immunohistochem Mol Morphol 2002, 10:139-146.
102. Shah T., Hochhauser D., Frow R., et al. Epidermal growth factor receptor expression and activation in neuroendocrine tumours. JNeuroendocrinol 2006, 18:355-360.
103. Wong W.M., Wright N.A. Cell proliferation in gastrointestinal mucosa. JClin Pathol 1999, 52:321-333.
104. Bouwens L., Kloppel G. Islet cell neogenesis in the pancreas. Virchows Arch 1996, 427:553-560.
105. Knudson A.G. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 1971, 68:820-823.
106. Vogelstein B., Kinzler K.W. Cancer genes and the pathways they control. Nat Med 2004, 10:789-799.
107. Berger A.H., Knudson A.G., Pandolfi P.P. Acontinuum model for tumour suppression. Nature 2011, 476:163-169.
108. Roche B., Sprouffske K., Hbid H., et al. Peto's paradox revisited: theoretical evolutionary dynamics of cancer in wild populations. Evol Appl 2013, 6:109-116.
109. Metz D.C., Jensen R.T. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 2008, 135:1469-1492.
110. Vortmeyer A.O., Huang S., Lubensky I., et al. Non-islet origin of pancreatic islet cell tumors. JClin Endocrinol Metab 2004, 89:1934-1938.
111. Oberg K., Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol 2005, 19:753-781.
112. Rindi G., Candusso M.E., Solcia E. Molecular aspects of the endocrine tumours of the pancreas and the gastrointestinal tract. Ital J Gastroenterol Hepatol 1999, 31(Suppl 2):S135-S138.
113. Yoshimoto K., Iwahana H., Fukuda A., et al. ras mutations in endocrine tumors: mutation detection by polymerase chain reaction-single strand conformation polymorphism. Jpn J Cancer Res 1992, 83:1057-1062.
114. Chamberlain C.E., Scheel D.W., McGlynn K., et al. Menin determines K-RAS proliferative outputs in endocrine cells. JClin Invest 2014, 124:4093-4101.
115. Leotlela P.D., Jauch A., Holtgreve-Grez H., et al. Genetics of neuroendocrine and carcinoid tumours. Endocr Relat Cancer 2003, 10:437-450.
116. Zhang J., Francois R., Iyer R., et al. Current understanding of the molecular biology of pancreatic neuroendocrine tumors. JNatl Cancer Inst 2013, 105:1005-1017.
117. Marinoni I., Kurrer A.S., Vassella E., et al. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology 2014, 146:453-460.e5.
118. Cao Y., Gao Z., Li L., et al. Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1. Nat Commun 2013, 4:2810.
119. He Y., Sandoval J., Casaccia-Bonnefil P. Events at the transition between cell cycle exit and oligodendrocyte progenitor differentiation: the role of HDAC and YY1. Neuron Glia Biol 2007, 3:221-231.
120. Speel E.J., Richter J., Moch H., et al. Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization. Am J Pathol 1999, 155:1787-1794.
121. Speel E.J., Scheidweiler A.F., Zhao J., et al. Genetic evidence for early divergence of small functioning and nonfunctioning endocrine pancreatic tumors: gain of 9Q34 is an early event in insulinomas. Cancer Res 2001, 61:5186-5192.
122. Rigaud G., Missiaglia E., Moore P.S., et al. High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications. Cancer Res 2001, 61:285-292.
123. Zhao J., Moch H., Scheidweiler A.F., et al. Genomic imbalances in the progression of endocrine pancreatic tumors. Genes Chromosomes Cancer 2001, 32:364-372.
124. Chung D.C., Brown S.B., Graeme-Cook F., et al. Overexpression of cyclin D1 occurs frequently in human pancreatic endocrine tumors. JClin Endocrinol Metab 2000, 85:4373-4378.
125. Chung D.C., Brown S.B., Graeme-Cook F., et al. Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors. Cancer Res 1998, 58:3706-3711.
126. Perren A., Komminoth P., Saremaslani P., et al. Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 2000, 157:1097-1103.
127. Missiaglia E., Dalai I., Barbi S., et al. Pancreatic endocrine tumors: expression profiling evidences a role for Akt-mTOR pathway. JClin Oncol 2010, 28:245-255.
128. Hu W., Feng Z., Modica I., et al. Gene amplifications in well-differentiated pancreatic neuroendocrine tumors inactivate the p53 pathway. Genes Cancer 2010, 1:360-368.
129. D'Adda T., Bottarelli L., Azzoni C., et al. Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. Mod Pathol 2005, 18:795-805.
130. Ghimenti C., Lonobile A., Campani D., et al. Microsatellite instability and allelic losses in neuroendocrine tumors of the gastro-entero-pancreatic system. Int J Oncol 1999, 15:361-366.
131. Arnold C.N., Sosnowski A., Blum H.E. Analysis of molecular pathways in neuroendocrine cancers of the gastroenteropancreatic system. Ann NY Acad Sci 2004, 1014:218-219.
132. Banck M.S., Kanwar R., Kulkarni A.A., et al. The genomic landscape of small intestine neuroendocrine tumors. JClin Invest 2013, 15.
133. Francis J.M., Kiezun A., Ramos A.H., et al. Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 2013, 45:1483-1486.
134. Warth A., Kloor M., Schirmacher P., et al. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP. Mod Pathol 2011, 24:564-570.
135. Kidd M., Eick G., Shapiro M.D., et al. Microsatellite instability and gene mutations in transforming growth factor-beta type II receptor are absent in small bowel carcinoid tumors. Cancer 2005, 103:229-236.
136. Lee M., Pellegata N.S. Multiple endocrine neoplasia syndromes associated with mutation of p27. JEndocrinol Invest 2013, 36:781-787.
137. Karnik S.K., Hughes C.M., Gu X., et al. Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27Kip1 and p18INK4c. Proc Natl Acad Sci U S A 2005, 102:14659-14664.
138. Vijayvergia N, Boland P, Gustafson K, etal. Molecular profiling of advanced stage neuroendocrine tumors (NETs): the Fox Chase Cancer Center (FCCC) experience. Poster presented at the 2015 Gastrointestinal Cancers Symposium, San Francisco, Jan 15-17, 2015; abstract 245; NANETs Abstract Handbook 2014, abstract BT13. Available at: http://meetinglibrary.asco.org/content/139139-158.
139. Tonnies H., Toliat M.R., Ramel C., et al. Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by comparative genomic hybridisation. Gut 2001, 48:536-541.
140. Kytola S., Hoog A., Nord B., et al. Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. Am J Pathol 2001, 158:1803-1808.
141. Kytola S., Nord B., Elder E.E., et al. Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. Genes Chromosomes Cancer 2002, 34:325-332.
142. Lollgen R.M., Hessman O., Szabo E., et al. Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer 2001, 92:812-815.
143. Andersson E., Sward C., Stenman G., et al. High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids. Endocr Relat Cancer 2009, 16:953-966.
144. Kulke M.H., Freed E., Chiang D.Y., et al. High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer 2008, 47:591-603.
145. Fearon E.R., Pierceall W.E. The deleted in colorectal cancer (DCC) gene: a candidate tumour suppressor gene encoding a cell surface protein with similarity to neural cell adhesion molecules. Cancer Surv 1995, 24:3-217.
146. Petzmann S., Ullmann R., Halbwedl I., et al. Analysis of chromosome-11 aberrations in pulmonary and gastrointestinal carcinoids: an array comparative genomic hybridization-based study. Virchows Arch 2004, 445:151-159.
147. Walsh K.M., Choi M., Oberg K.E., et al. Apilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum. Endocr Relat Cancer 2011, 18:171-180.
148. Muneyuki T., Watanabe M., Yamanaka M., et al. Combination analysis of genetic alterations and cell proliferation in small intestinal carcinomas. Dig Dis Sci 2000, 45:2022-2028.
149. Planck M., Ericson K., Piotrowska Z., et al. Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine. Cancer 2003, 97:1551-1557.
150. Bloomston M., Durkin A., Yang I., et al. Identification of molecular markers specific for pancreatic neuroendocrine tumors by genetic profiling of core biopsies. Ann Surg Oncol 2004, 11:413-419.
151. Duerr E.M., Mizukami Y., Ng A., et al. Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. Endocr Relat Cancer 2008, 15:243-256.
152. Kidd M., Modlin I.M., Mane S.M., et al. The role of genetic markers-NAP1L1, MAGE-D2, and MTA1-in defining small-intestinal carcinoid neoplasia. Ann Surg Oncol 2006, 13:253-262.
153. Hofer M.D., Tapia C., Browne T.J., et al. Comprehensive analysis of the expression of the metastasis-associated gene 1 in human neoplastic tissue. Arch Pathol Lab Med 2006, 130:989-996.
154. Drozdov I., Kidd M., Nadler B., et al. Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learning. Cancer 2009, 115:1638-1650.
155. Leja J., Essaghir A., Essand M., et al. Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol 2009, 22:261-272.
156. Cui T., Hurtig M., Elgue G., et al. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors. PLoS ONE 2010, 5:e16010.
157. Edfeldt K., Bjorklund P., Akerstrom G., et al. Different gene expression profiles in metastasizing midgut carcinoid tumors. Endocr Relat Cancer 2011, 18:479-489.
158. Kidd M., Modlin I.M., Drozdov I. Gene network-based analysis identifies two potential subtypes of small intestinal neuroendocrine tumors. BMC Genomics 2014, 15:595.
159. Drozdov I., Svejda B., Gustafsson B., et al. Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia. PloS ONE 2011, 6:e22457.
160. Roldo C., Missiaglia E., Hagan J.P., et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. JClin Oncol 2006, 24:4677-4684.
161. Thorns C., Schurmann C., Gebauer N., et al. Global MicroRNA profiling of pancreatic neuroendocrine neoplasias. Anticancer Res 2014, 34:2249-2254.
162. Li A., Yu J., Kim H., et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res 2013, 19:3600-3610.
163. Li S.C., Essaghir A., Martijn C., et al. Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors. Mod Pathol 2013, 26:685-696.
164. Ruebel K., Leontovich A.A., Stilling G.A., et al. MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression. Mod Pathol 2010, 23:367-375.
165. Jarhult J., Landerholm K., Falkmer S., et al. First report on metastasizing small bowel carcinoids in first-degree relatives in three generations. Neuroendocrinology 2010, 91:318-323.
166. Larsson C., Skogseid B., Oberg K., et al. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 1988, 332:85-87.
167. Boissan M., De Wever O., Lizarraga F., et al. Implication of metastasis suppressor NM23-H1 in maintaining adherens junctions and limiting the invasive potential of human cancer cells. Cancer Res 2010, 70:7710-7722.
168. Hendy G.N., Kaji H., Sowa H., et al. Menin and TGF-beta superfamily member signaling via the Smad pathway in pituitary, parathyroid and osteoblast. Horm Metab Res 2005, 37:375-379.
169. Gurung B., Feng Z., Hua X. Menin directly represses Gli1 expression independent of canonical Hedgehog signaling. Mol Cancer Res 2013, 11:1215-1222.
170. Yang Y.J., Song T.Y., Park J., et al. Menin mediates epigenetic regulation via histone H3 lysine 9 methylation. Cell Death Dis 2013, 4:e583.
171. Hughes C.M., Rozenblatt-Rosen O., Milne T.A., et al. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Mol Cell 2004, 13:587-597.
172. Matkar S., Thiel A., Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci 2013, 38:394-402.
173. Richard S., Giraud S., Beroud C., et al. Maladie de von Hippel-Lindau: progrès génétiques récents et prise en charge des patients. [Von Hippel-Lindau disease: recent genetic progress and patient management.] Francophone Study Group of von Hippel-Lindau Disease (GEFVH). Ann Endocrinol (Paris) 1998, 59:452-458. [in French].
174. Kibel A., Iliopoulos O., DeCaprio J.A., et al. Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science 1995, 269:1444-1446.
175. Bluyssen H.A., Lolkema M.P., van Beest M., et al. Fibronectin is a hypoxia-independent target of the tumor suppressor VHL. FEBS Lett 2004, 556:137-142.
176. Ruggieri M., Huson S.M. The neurofibromatoses. An overview. Ital J Neurol Sci 1999, 20:89-108.
177. Au K.S., Williams A.T., Gambello M.J., et al. Molecular genetic basis of tuberous sclerosis complex: from bench to bedside. JChild Neurol 2004, 19:699-709.
178. Zikusoka M.N., Kidd M., Eick G., et al. The molecular genetics of gastroenteropancreatic neuroendocrine tumors. Cancer 2005, 104:2292-2309.
179. Calender A. Molecular genetics of neuroendocrine tumors. Digestion 2000, 62(Suppl 1):3-18.
180. Hiripi E., Bermejo J.L., Sundquist J., et al. Familial gastrointestinal carcinoid tumours and associated cancers. Ann Oncol 2009, 20:950-954.
181. Hemminki K., Li X. Familial carcinoid tumors and subsequent cancers: a nation-wide epidemiologic study from Sweden. Int J Cancer 2001, 94:444-448.
182. Hassan M.M., Phan A., Li D., et al. Family history of cancer and associated risk of developing neuroendocrine tumors: a case-control study. Cancer Epidemiol Biomarkers Prev 2008, 17:959-965.
183. Sun M., Guo X., Qian X., et al. Activation of the ATM-Snail pathway promotes breast cancer metastasis. JMol Cell Biol 2012, 4:304-315.
184. Lee J., Sung C.O., Lee E.J., et al. Metastasis of neuroendocrine tumors are characterized by increased cell proliferation and reduced expression of the ATM gene. PLoS ONE 2012, 7:e34456.
185. Shin J.U., Lee C.H., Lee K.T., et al. Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor. Tumour Biol 2012, 33:1645-1651.
186. Li D.Q., Pakala S.B., Nair S.S., et al. Metastasis-associated protein 1/nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res 2012, 72:387-394.
187. Azzoni C., Bottarelli L., Cecchini S., et al. Involvement of HER-2/neu and metastasis-related proteins in the development of ileal neuroendocrine tumors. Virchows Arch 2011, 458:525-536.
188. Sundin A. Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol 2012, 26:803-818.
189. Reubi J.C., Maurer R., von Werder K., et al. Somatostatin receptors in human endocrine tumors. Cancer Res 1987, 47:551-558.
190. Nilsson O., Kolby L., Wangberg B., et al. Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours. Br J Cancer 1998, 77:632-637.
191. Bodei L., Sundin A., Kidd M., et al. The status of neuroendocrine tumor imaging: from darkness to light?. Neuroendocrinology 2014, Published online. http://dx.doi.org/10.1159/000367850.
192. Pearse A.G. 5-hydroxytryptophan uptake by dog thyroid 'C' cells, and its possible significance in polypeptide hormone production. Nature 1966, 211:598-600.
193. Neels O.C., Koopmans K.P., Jager P.L., et al. Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3,4-dihydroxy-l-phenylalanine accumulation in neuroendocrine tumor cells. Cancer Res 2008, 68:7183-7190.
194. Blackmore C.G., Varro A., Dimaline R., et al. Measurement of secretory vesicle pH reveals intravesicular alkalinization by vesicular monoamine transporter type 2 resulting in inhibition of prohormone cleavage. JPhysiol 2001, 531:605-617.
195. Kolby L., Bernhardt P., Levin-Jakobsen A.M., et al. Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters. Br J Cancer 2003, 89:1383-1388.
196. Baum R.P., Kulkarni H.R., Carreras C. Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms. Semin Nucl Med 2012, 42:190-207.
197. 18F-DOPA PET: a prospective, diagnostic accuracy study. Lancet Oncol 2006, 7:728-734.
198. 11C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography. JClin Endocrinol Metab 2005, 90:3392-3400.
199. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res 2010, 16:978-985.
200. Grozinsky-Glasberg S., Pavel M. Inhibition of mTOR in carcinoid tumors. Target Oncol 2012, 7:189-195.
201. Cierpicki T., Grembecka J. Challenges and opportunities in targeting the menin-MLL interaction. Future Med Chem 2014, 6:447-462.
202. Shi A., Murai M.J., He S., et al. Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia. Blood 2012, 120:4461-4469.
203. Mohammad K.S., Javelaud D., Fournier P.G., et al. TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res 2011, 71:175-184.
204. Della Gatta G., Palomero T., Perez-Garcia A., et al. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL. Nat Med 2012, 18:436-440.
205. Piccaluga P.P., De Falco G., Kustagi M., et al. Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes. Blood 2011, 117:3596-3608.
206. Modlin I.M., Gustafsson B.I., Drozdov I., et al. Principal component analysis, hierarchical clustering, and decision tree assessment of plasma mRNA and hormone levels as an early detection strategy for small intestinal neuroendocrine (carcinoid) tumors. Ann Surg Oncol 2009, 16:487-498.
207. Modlin I., Drozdov I., Kidd M. Amultitranscript blood neuroendocrine tumor molecular signature to identify treatment efficacy and disease progress. JClin Oncol 2013, 31(Suppl):A4137.
208. Modlin I.M., Drozdov I., Bodei L., et al. Blood transcript analysis and metastatic recurrent small bowel carcinoid management. BMC Cancer 2014, 14:564.
209. Modlin I., Drozdov I., Alaimo D., et al. Amultianalyte PCR blood test outperforms single analyte ELISAs for neuroendocrine tumor detection. Endocr Relat Cancer 2014, 21:615-628.
210. Modlin I., Drozdov I., Kidd M. The identification of gutneuroendocrine tumor disease by multiple synchronous transcript analysis in blood. PloS ONE 2013, e63364.
211. Modlin I., Drozdov I., Kidd M. Gut neuroendocrine tumor blood qPCR fingerprint assay: characteristics and reproducibility. Clin Chem 2014, 52:419-429.
212. Modlin I.M., Aslanian H., Bodei L., et al. APCR blood test outperforms chromogranin A in carcinoid detection and is unaffected by PPIs. Endocr Connect 2014, 3:215-223.
213. Franceschini A., Szklarczyk D., Frankild S., et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013, 41:D808-D815.