Neuroendocrine tumours of the gastroenteropancreatic tract (GEP NETs) represent a rare and heterogeneous group of tumours. Based on their ontogenetic origin, GEP NETs are classified into foregut, midgut and hindgut tumours. Although they have many features in common, their molecular backgrounds are obviously different. Elucidation of the key factors determining tumour biology has been hampered by the low incidence and high variability of these tumours in terms of origin, morphology and growth. However, recent years have shed some light on molecular genetics of these tumours, revealing important genetic factors as the RET proto-oncogene and the tumour suppressor menin as well as knowledge about the role of growth factors like IGF-1, TGF-β, VEGF and PDGF for the regulation of differentiation, growth and secretion. In the future, emerging molecular tools in rapid individual genome analysis and in proteomic and array technologies may help to delineate common patterns of NET disease.

1.
Rindi G, Villanacci V, Ubiali A: Biological and molecular aspects of gastroenteropancreatic neuroendocrine tumors. Digestion 2000;62(suppl 1):19–26.
2.
Bartsch D, Hahn SA, Danichevski KD, Ramaswamy A, Bastian D, Galehdari H, Barth P, Schmiegel W, Simon B, Rothmund M: Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors. Oncogene 1999;18:2367–2371.
3.
Muscarella P, Melvin WS, Fisher WE, Foor J, Ellison EC, Herman JG, Schirmer WJ, Hitchcock CL, DeYoung BR, Weghorst CM: Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: An analysis of p16/MTS1 tumor suppressor gene inactivation. Cancer Res 1998;58:237–240.
4.
Lubomierski N, Kersting M, Bert T, Muench K, Wulbrand U, Schuermann M, Bartsch D, Simon B: Tumor suppressor genes in the 9p21 gene cluster are selective targets of inactivation in neuroendocrine gastroenteropancreatic tumors. Cancer Res 2001;61:5905–5910.
5.
Lollgen RM, Hessman O, Szabo E, Westin G, Akerstrom G: Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer 2001;92:812–815.
6.
Jensen RT: Carcinoid and pancreatic endocrine tumors: Recent advances in molecular pathogenesis, localization, and treatment. Curr Opin Oncol 2000;12:368–377.
7.
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.
8.
Calender A: Molecular genetics of neuroendocrine tumors. Digestion 2000;62(suppl 1):3–18.
9.
Ichihara M, Murakumo Y, Takahashi M: RET and neuroendocrine tumors. Cancer Lett 2004;204:197–211.
10.
Ludwig L, Kessler H, Hoang-Vu C, Dralle H, Adler G, Boehm BO, Schmid RM: Grap-2, a novel RET binding protein, is involved in RET mitogenic signaling. Oncogene 2003;22:5362–5366.
11.
Rindi G, Capella C, Solcia E: Cell biology, clinicopathological profile, and classification of gastro-enteropancreatic endocrine tumors. J Mol Med 1998;76:413–420.
12.
Wiedenmann B, John M, Ahnert-Hilger G, Riecken EO: Molecular and cell biological aspects of neuroendocrine tumors of the gastroenteropancreatic system. J Mol Med 1998;76:637–647.
13.
Bast RC, Kufe DW, Pollock RE, et al: Neoplasms of the Endocrine Glands. Cancer Medicine, ed 5. Hamilton, BC Decker Inc, 2000.
14.
Modlin IM, Sandor A: An analysis of 8,305 cases of carcinoid tumors. Cancer 1997;79:813–829.
15.
John M, Meyerhof W, Richter D, Waser B, Schaer JC, Scherubl H, Boese-Landgraf J, Neuhaus P, Ziske C, Molling K, Riecken EO, Reubi JC, Wiedenmann B: Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2. Gut 1996;38:33–39.
16.
Schaer JC, Waser B, Mengod G, Reubi JC: Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: Comparison of mRNA analysis with receptor autoradiography. Int J Cancer 1997;70:530–537.
17.
Kulaksiz H, Eissele R, Rossler D, Schulz S, Hollt V, Cetin Y, Arnold R: Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype-specific antibodies. Gut 2002;50:52–60.
18.
Reubi JC, Waser B: Concomitant expression of several peptide receptors in neuroendocrine tumours: Molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging 2003;30:781–793.
19.
von Wichert G, Jehle PM, Hoeflich A, Koschnick S, Dralle H, Wolf E, Wiedenmann B, Boehm BO, Adler G, Seufferlein T: Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res 2000;60:4573–4581.
20.
Chaudhry A, Oberg K, Gobl A, Heldin CH, Funa K: Expression of transforming growth factors beta 1, beta 2, beta 3 in neuroendocrine tumors of the digestive system. Anticancer Res 1994;14:2085–2091.
21.
Chaudhry A, Papanicolaou V, Oberg K, Heldin CH, Funa K: Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Cancer Res 1992;52:1006–1012.
22.
Chaudhry A, Funa K, Oberg K: Expression of growth factor peptides and their receptors in neuroendocrine tumors of the digestive system. Acta Oncol 1993;32:107–114.
23.
Peghini PL, Iwamoto M, Raffeld M, Chen YJ, Goebel SU, Serrano J, Jensen RT: Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability. Clin Cancer Res 2002;8:2273–2285.
24.
Wulbrand U, Wied M, Zofel P, Goke B, Arnold R, Fehmann H: Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours. Eur J Clin Invest 1998;28:1038–1049.
25.
Wimmel A, Wiedenmann B, Rosewicz S: Autocrine growth inhibition by transforming growth factor beta-1 (TGFbeta-1) in human neuroendocrine tumour cells. Gut 2003;52:1308–1316.
26.
von Marschall Z, Scholz A, Cramer T, Schafer G, Schirner M, Oberg K, Wiedenmann B, Hocker M, Rosewicz S: Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. J Natl Cancer Inst 2003;95:437–448.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.