Table of Contents
ISRN Neuroendocrinology
Volume 2012, Article ID 874350, 11 pages
Review Article

Profiling of GEPNETs

Sahlgrenska Cancer Centre and Department of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden

Received 26 September 2011; Accepted 20 October 2011

Academic Editors: Y. J. Chen, S. De Dosso, G. Procopio, and D. van West

Copyright © 2012 Ola Nilsson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The tumorigenesis of gastrointestinal and pancreatic tumors (GEPNETs) is poorly understood. We need a better understanding of the molecular alterations in GEPNETs to obtain an accurate classification, and it may also provide targets for therapeutic intervention. Purpose of Paper. The purpose of this paper was to critically examine recent advances in the molecular understanding of GEPNETs gained from genome-wide and transcriptome-wide profiling studies. Special emphasis was put on diagnostic, predictive, and therapeutic implications of profiling studies. Results. Pancreatic neuroendocrine tumours (PNETs) were characterised by a distinct pattern of chromosomal alterations and a higher degree of chromosomal instability (CIN) than ileal carcinoids. Subgroups of PNETs and ileal carcinoids were identified on the basis of specific chromosomal alterations. Exome sequencing identified mutations in MEN1, ATRX/DAXX, and mTOR pathway genes as being frequent events in sporadic PNETs. Expression profiles of PNETs and ileal carcinoids were found to be different, and allowed identification of subgroups of tumors, as well discrimination between benign and malignant tumors. The molecular data provided a number of candidate genes and pathways suitable for targeted therapy. For PNETs, candidate targets include BRAF, KRAS, TERT, EGFR, RET, MDM2, IGF, MET/HGF, ANG2, LCK, PDGFRB, AKT-mTOR, and SSTR2. Some of these targets have already been evaluated in clinical trials (mTOR and SSTR2). For ileal carcinoids, significantly fewer candidate targets were provided, including ERBB2 (HER2), RET, APLP1, and Notch. Conclusion. Profiling of GEPNETs is a powerful tool for discovery of novel targets for therapeutic intervention. Further studies, combining genome, epigenome, transcriptome, and proteome data are needed to enable us to identify clinically relevant targets in GEPNETs.